RxPG News : Breast Cancer

Acupuncture has added benefits in breast cancer patients

Wed, 30 Dec 2009 13:36:51 PST

( from http://www.rxpgnews.com ) Not only is acupuncture as effective as drug therapy at reducing hot flushes in breast cancer patients, it has the added benefit of potentially increasing a woman's sex drive and improving her sense of well-being, according to a Henry Ford Hospital study.

Study results show that acupuncture, when compared to drug therapy, has a longer-lasting effect on the reduction of hot flushes and night sweats for women receiving hormone therapy for breast cancer treatment. Women also report that acupuncture improves their energy and clarity of thought.

The study, published online this week in the Journal of Oncology, is the first randomly controlled trial to compare acupuncture and drug therapy in this way.

"Acupuncture offers patients a safe, effective and durable treatment option for hot flushes, something that affects the majority of breast cancer survivors. Compared to drug therapy, acupuncture actually has benefits, as opposed to more side effects," says study lead author Eleanor Walker, M.D., division director of breast services in the Department of Radiation Oncology at Henry Ford Hospital.

According to the National Cancer Institute, one in eight women will develop breast cancer in her lifetime. For these women, conventional medical treatment involves chemotherapy and five years of hormone therapy. With such a long course of treatment, side effects of hormone therapy such as vasomotor symptoms – hot flushes and night sweats – can become a major cause of decreased quality of life, and even discontinuation of treatment.

Venlafaxine (Effexor) has been the drug therapy of choice to manage these common and debilitating side effects associated with breast cancer treatment. Venlafixine, however, comes with its own set of side-effects: dry mouth, decreased appetite, nausea and constipation.

Since acupuncture has been shown to effectively reduce hot flushes in menopausal women, Dr. Walker and her research team decided to test the use of acupuncture to combat vasomotor symptoms in breast cancer patients as an alternative to drug therapy.

To compare the two options, 50 patients were recruited from oncology clinics at Henry Ford. Patients were randomly assigned to receive either acupuncture or venlafaxine treatment for 12 weeks. The drug therapy group took venlafaxine orally each night, 37.5mg the first week and then 75mg for the remaining 11 weeks. The other group received acupuncture treatments twice per week for the first four weeks, and then once a week for the remaining eight weeks.

At the end of 12 weeks, all patients stopped their therapy and were followed for one year. Patients kept a diary to record the number and severity of hot flushes, and took surveys to measure their overall health and mental health.

The study found that both groups initially experienced a 50 percent decline in hot flushes and depressive symptoms, indicating that acupuncture is as effective as drug therapy.

Differences, however, between the two groups began to emerge two weeks post-treatment: The acupuncture group continued to experience minimal hot flushes, while the drug therapy group had a significant increase in hot flashes. The acupuncture group did not experience an increase in the frequency of their hot flushes until three months post-treatment.

Study finds higher risk of cancer recurrence in women with dense breasts

Tue, 10 Nov 2009 12:14:32 PST

( from http://www.rxpgnews.com ) Women with heavier busts who have been treated for breast cancer are at higher risk of its recurrence, says a new study.

These findings indicate that such patients may benefit from additional therapies, such as radiation, following surgery.

Researchers suspected that high breast density - may also increase the risk of cancer recurrence after lumpectomy, but this theory has not been thoroughly studied.

Lumpectomy is a surgical procedure that involves removing a suspected malignant - tumour, or lump, and a small portion of the surrounding tissue from a woman's breast.

Researchers led by Steven A. Narod, Women's College Research Institute - in Toronto reviewed the medical records of 335 patients who had undergone lumpectomy for breast cancer.

Researchers found that patients with the highest breast density had a much greater risk of cancer recurrence than did women with the lowest breast density.

Over 10 years, women in the highest breast density category had a 21 percent chance of cancer recurrence, compared to a five percent chance among women in the lowest category, according to a WCRI release.

'The composition of the breast tissue surrounding the breast cancer is important in predicting whether or not a breast cancer will return after surgery,' Narod said.

The study authors say their findings indicate that women with low breast density, who have a low chance of recurrence after surgery, may not need radiation but that women with high breast density could significantly benefit from the additional therapy.

These findings are slated for publication in December issue of Cancer, a journal of the American Cancer Society.

Physical activity after menopause reduces breast cancer

Thu, 15 Jan 2009 15:11:57 PST

( from http://www.rxpgnews.com ) Several studies had previously suggested that regular physical exercise reduces the breast cancer risk of women. However, it had been unknowned just how much exercise women should take in which period in life in order to benefit from this protective effect. Moreover, little was known about which particular type of breast cancer is influenced by physical activity.

Answers to these questions are now provided by the results of the MARIE study, in which 3,464 breast cancer patients and 6,657 healthy women between the ages of 50 and 74 years were questioned in order to explore the connections between life style and breast cancer risk. Participants of the study, which was headed by Professor Dr. Jenny Chang-Claude and conducted at the German Cancer Research Center and the University Hospitals of Hamburg-Eppendorf, were questioned about their physical activity during two periods in life: from 30 to 49 years of age and after 50.

A comparison between control subjects and breast cancer patients showed that women in the control group had been physically more active than patients. The scientists calculated the relative breast cancer risks taking account of the effect of other risk factors. Results show that the risk of developing breast cancer after menopause was lower by about one third in the physically most active MARIE participants compared to women who had generally taken little physical exercise.

For this reduced risk it is not necessary to work out hard at the gym. The women in the physically most active group, for example, walked for two hours every day and cycled for one hour, while the most inactive study participants walked for only about 30 minutes every day. The epidemiologists also discovered that physical activity in the postmenopausal period is particularly beneficial for reducing breast cancer risk.

A closer look at the types of breast cancer revealed that physically active women are less frequently affected, in particular, by tumors that form receptors for the two female sexual hormones, estrogen and progesterone. These malignant 'hormone receptor positive tumors' accounted for 62.5 percent of breast cancers among MARIE participants. Other tumor markers, such as HER2 receptor formation or differentiation stage of cancer cells, were found to be unrelated to physical activity.

The effect of physical activity was independent of weight gain, total energy intake or body mass index. Therefore, researchers assume that physical exercise reduces the risk of cancer through hormonal mechanisms instead merely by a reduction of body fat or other changes in physical constitution, as it has often been assumed.

"It doesn't always have to be sports," says Associate Professor Dr. Karen Steindorf of DKFZ, who has headed this analysis. "In our calculations we have also taken account of activities such as gardening, cycling or walking to the shops. Our advice to all women is therefore to stay or become physically active also in the second half of your life. You will not only reduce your risk of breast cancer, but it has been proven that your bones, heart and brain also benefit from it."

Genes responsible for susceptibility to breast cancer metastasis can be inherited

Sun, 04 Jan 2009 14:06:55 PST

( from http://www.rxpgnews.com ) New research in mice and five independent collections of human breast tumors has enabled National Cancer Institute (NCI) scientists to confirm that genes for factors contributing to susceptibility for breast cancer metastasis can be inherited. The new findings support earlier results from the same laboratory and appear in the Jan. 1, 2009, issue of Cancer Research.

The study results also show that gene activities in tumor cells and immune cells that infiltrate, or invade, tumors can contribute to the development of expression profiles, called gene signatures, that are predictive of cancer progression. The analysis of normal mouse tissue as well as tumors transplanted into mice suggests that predictive, or prognostic, gene signatures that point to a tumor's potential for spreading throughout the body can be the result of both inherited and non-inherited factors, with inherited factors being more consistently predictive. The research team that reported these findings is from the Center for Cancer Research at NCI, which is part of the National Institutes of Health.

The researchers were able to perform their analyses by using advances in microarray technology, which allows scientists to scan vast amounts of genetic information and identify gene signatures that can be used to predict cancer outcomes. Many scientists had assumed that metastatic ability is primarily determined by somatic, or non-inherited, gene mutations in tumor tissue. "Our earlier studies clearly established that inherited factors also play an important role in metastatic progression and can help distinguish which tumors have a propensity to metastasize," said author Kent W. Hunter, Ph.D., head of NCI's Metastasis Susceptibility Section in the Laboratory of Cancer Biology and Genetics. "Hopefully in the future we will be able to determine which women are more likely to have a tumor that would metastasize, and we could then tailor therapy specifically for them, avoiding the use of harsh treatments for those with a low probability of metastasis."

To determine whether mouse tumor gene expression profiles could be used to predict outcomes in human breast cancer, the investigators identified a gene expression signature that allowed them to distinguish between the tumors of mice that have a high or a low inherited susceptibility to tumor metastasis (a 20-fold difference). They then converted the mouse gene signature to the corresponding human gene signature and analyzed five pre-existing sets of human breast tumors. This signature successfully predicted outcomes (either relapse or disease-free survival) in four of the five sets of human breast tumors.

Because other studies have suggested that gene expression patterns in the nearby tissue, or stroma, are altered in tumors that are prone to metastasis, the investigators conducted transplant experiments by putting highly metastatic tumor cells into the mammary fat pads of mice that have either a high or a low susceptibility to tumor metastasis. These transplants resulted in tumors that had identical tumor cells but different stroma and immune cells that infiltrated the tumor. No significant differences were seen in tumor weight or metastasis to the lung in the two types of mice after 28 days, suggesting that metastatic differences between individual mice in this experiment were possibly due to genes in the outer layer of tissue that surrounds the tumor (the epithelium) rather than in the stroma. However, differences in gene signatures were still seen in mice with either high or low potential to develop metastases, and the corresponding human genes signatures were predictive of relapse or survival in patients. The researchers concluded that both the tumor epithelium and the stroma probably contributed to the development of the prognostic gene profiles.

"Our study provides additional evidence of the role of inherited genes in human breast cancer progression. Therefore our next step is to improve our current understanding of the role of the epithelium and stroma in tumor progression and develop more effective therapeutic strategies based on our new knowledge," said Hunter.

Oestrogen therapy of benefit in some women with metastatic cancer

Fri, 12 Dec 2008 13:43:25 PST

( from http://www.rxpgnews.com ) For breast cancer survivors, the idea of taking estrogen pills is almost a taboo. In fact, their doctors give them drugs to get rid of the hormone because it can fuel the growth of breast cancer. So these women would probably be surprised by the approach taken by breast cancer physician Matthew Ellis, M.B., Ph.D., associate professor of medicine at Washington University School of Medicine in St. Louis — he has demonstrated that estrogen therapy can help control metastatic breast cancer.

In a study presented at the 31st annual San Antonio Breast Cancer Symposium, he showed that for about a third of the 66 participants — women with metastatic breast cancer that had developed resistance to standard estrogen-lowering therapy — a daily dose of estrogen could stop the growth of their tumors or even cause them to shrink. The study was funded by the Avon Foundation through the National Cancer Institute and included six cancer centers in the United States.

Ellis believes that estrogen therapy offers an appealing alternative to chemotherapy for metastatic breast cancer that has become resistant to estrogen-lowering agents called aromatase inhibitors, such as exemestane, anastrazole and letrozole. These drugs deplete the body of estrogen and are standard treatments for hormone-receptor positive breast cancers, which account for about 75 percent of breast cancer cases.

"By stabilizing or shrinking tumors in some women with metastatic breast cancer, estrogen therapy can relieve pain and other symptoms of cancer and can potentially prolong lives," says Ellis, an oncologist with the Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital. "And unlike chemotherapy, estrogen enhances the quality of life. For many of our patients, their hot flashes disappear, and they lose other symptoms of menopause. It's a natural treatment for breast cancer. Not only that, it's much cheaper than chemotherapy, costing less than a dollar a day."

Furthermore, estrogen seems able to return metastatic tumors to a vulnerable state in which they again can be affected by aromatase inhibitors. "We thought acquired resistance to aromatase inhibitor therapy was permanent," Ellis says. "But now we've shown that in some patients giving estrogen can make it possible to cycle back to aromatase inhibitors, and they can work again."

About 40,000 women die of metastatic breast cancer each year, and estrogen therapy potentially could help thousands of women with hormone receptor-positive disease, Ellis says.

The study measured how many women with aromatase inhibitor therapy-resistant metastatic breast cancer responded to estrogen therapy. All study participants had estrogen-receptor positive tumors that had spread to their bones, livers or lungs. The women were postmenopausal with an average age of 59.

Coming into the study, all the participants were taking aromatase inhibitors to slow or stop the growth of their tumors. But their tumors had stopped responding to the treatment and had begun to grow again. Half of the patients got a high dose of estrogen (30 milligrams a day) and half got a low dose (6 milligrams a day).

Ellis points out that decades ago, high-dose synthetic estrogen was an accepted breast cancer therapy and was only abandoned when the estrogen-blocker tamoxifen came along in the 1970s and proved just as effective with fewer side effects. The high dose in the current study was based on the amount given to breast cancer patients in many of those earlier regimens.

Both the high- and low-dose treatments led to stabilization or shrinkage of metastatic tumors in about 30 percent of the participants. But the high-dose regimen had significant side effects such as nausea, vomiting, vaginal bleeding, fluid retention or calcium imbalances. In contrast, the low-dose regimen had few side effects and was well tolerated.

The researchers found that if study participants eventually experienced disease progression on estrogen, they could go back to an aromatase inhibitor that they were previously resistant to and see a benefit — their tumors were once again inhibited by estrogen deprivation. That effect sometimes wore off after several months, but then the tumors might again be sensitive to estrogen therapy. In fact, some patients have cycled back and forth between estrogen and an aromatase inhibitor for several years, thereby managing their metastatic disease.

The researchers also found that PET (positron emission tomography) scans could predict whose tumors would respond to estrogen therapy. They measured tumor glucose uptake before starting the women on estrogen and again 24 hours later. The patients whose tumors showed an increased glucose uptake, called a PET flare, were the same patients who benefited from estrogen therapy.

It's too early to know why estrogen has a negative effect on metastatic breast cancer tumors. But Ellis has found one clue — estrogen reduces the amount of a tumor-promoting hormone called insulin-like growth factor-1 (IGF1).

"I think that in order for breast cancer cells to survive in the absence of estrogen (when patients are on aromatase inhibitors), the cells have to learn to alter their cellular programs to utilize alternative growth signals like IGF1," Ellis says. "In theory, when you give estrogen back, IGF1 decreases and cancer cells die as a consequence. But surviving cancer cells prefer to switch back to living on estrogen — to them it's like eating out at McDonald's every day instead of foraging on roots and berries. These cells eventually reappear as estrogen dependent tumors and the cycle starts over."

Ellis plans to continue to follow metastatic breast cancer patients to quantify the response rate to retreatment with aromatase inhibitors when estrogen therapy stops working.

Awry protein linked to breast cancer

Thu, 09 Oct 2008 09:40:48 PST

( from http://www.rxpgnews.com ) Sydney, Oct 9 - A developmental protein like Notch that sometimes goes awry has been linked to breast cancer, according to a new study.

The breast cancer team at Walter and Eliza Hall Institute of Medical Research -, led by Jane Visvader and Geoff Lindeman from the Victorian Breast Cancer Research Consortium, have identified important roles for Notch genes in regulating breast development and function.

This discovery has important implications for breast cancer, since elevated levels of Notch have been linked to breast cancer. The advance builds on the group's 2006 discovery of the breast stem cell in mice, according to a release.

Research carried out by Toula Bouras and colleagues has uncovered dual functions for Notch in breast tissue. First, Notch helps restrict breast stem cell number, so that when it is 'switched off', there is a resultant expansion in breast stem cells.

Second, Notch is important for ensuring that stem cells produce the sleeve of cells that normally line breast ducts. These 'luminal' cells may be the cells that give rise to common types of breast cancer, according to the WEHI release.

Thus, Notch helps to orchestrate the formation of breast tissue: it plays an important role in controlling stem cell numbers and instructs stem cells to produce luminal cells.

Significantly, Bouras and colleagues found that errant activation of Notch resulted in uncontrolled growth of luminal precursors, leading to the formation of breast tumours.

Ultrasound-guided fine needle aspiration (USFNA) of the lymph nodes is -a useful preoperative staging for breast cancer

Sat, 12 Apr 2008 10:08:40 PST

( from http://www.rxpgnews.com ) Ultrasound-guided fine needle aspiration (USFNA) of the lymph nodes is a safe, useful, and minimally invasive procedure for diagnosing metastatic disease in patients who are undergoing preoperative staging for breast cancer, according to a recent study conducted by researchers at the Rhode Island Hospital/Warren Alpert Medical School of Brown University in Providence, RI.

“We wanted to determine which patients with newly diagnosed breast cancer would benefit most from preoperative fine needle aspiration of the axillary lymph nodes,” said Martha Mainiero, MD, lead author of the study. “This quick and minimally invasive procedure can assist the surgeon in determining what type of axillary surgery is best for patients with breast cancer. Unfortunately many centers do not routinely perform this procedure as there is not yet consensus on who will benefit from it,” she said.

The study consisted of USFNA of axillary lymph nodes in 224 breast cancer patients. The researchers measured the cortical thickness of each lymph node that was aspirated. They found that using a cortical thickness measurement of 3mm to determine who gets USFNA would result in the most optimum combination of diagnosing metastatic disease preoperatively while minimizing unnecessary USFNA. Patients in the study had primary tumor sizes ranging from 0-12 cm with a mean of 1.9cm and included 159 tumors that measured less than or equal to 2 cm and 65 tumors that were greater than 2 cm. The use of USFNA was positive in 52 patients (23%). If USFNA were limited only to axillary lymph nodes with a cortical thickness of 3 mm or more, USFNA positivity would have increased to 49%.

“With these results, this procedure may become more widely used and save patients unnecessary surgery,” said Dr. Mainiero. “This cut-off provided the most optimum combination in detecting metastatic disease while minimizing negative USFNA results,” she said.

Screening mammography in elderly patients beneficial

Sat, 12 Apr 2008 03:59:37 PST

( from http://www.rxpgnews.com ) Although guidelines keep changing regarding screening mammography in elderly patients, those older than 70 years old continue to benefit from this exam, showing that with frequent mammograms breast cancers can be found sooner, according to a recent study conducted by researchers at Jacobi Medical Center and Albert Einstein College of Medicine, in Bronx, NY.

“Our initial interest was sparked by the changing mammographic guidelines in the elderly age group and the differences in the guidelines between organizations including the American Cancer Society and American College of Radiology,” said Jason Salsamendi, MD, lead author of the study. “We also noticed that we were performing a significant number of screening mammograms in elderly patients at our institution and became curious about the incidence of occult breast cancer in this age group,” he said.

The study consisted of the review of 24 cases of breast cancer in 22 elderly patients age 70-89.

The researchers evaluated the mammograms for masses and calcifications and correlated the results to surgically proven histology, lymph node involvement and initial surgical management.

According to the study, 19 of the 24 cases of breast malignancy were initially identified on screening mammography. The study showed that mammographic findings in these 19 cases included 12 masses, 4 suspicious calcifications and 3 masses with calcifications. Of these, surgical management was available in 18 cases with 15 being treated by lumpectomy and 3 being treated with mastectomy. The study also showed that the average time interval from most recent prior mammogram to diagnosis was 2.6 years.

“During our study, we found that five patients never had a prior mammogram. Their breast cancer was detected on a baseline study. These five patients included three cases of infiltrating ductal carcinoma,” said Dr. Salsamendi. “Perhaps with more frequent mammographic screening, more breast cancers can be found earlier, at a noninvasive stage. This would result in a less extensive surgical procedure and improve prognosis. Our results encourage clinicians to continue to order screening mammography in elderly patients at yearly intervals,” he said.

Obesity causes breast cancer to be aggressive

Fri, 14 Mar 2008 11:02:54 PST

( from http://www.rxpgnews.com ) Women with breast cancer have more aggressive disease and lower survival rates if they are overweight or obese, according to findings published in the March 15 issue of Clinical Cancer Research, a journal of the American Association for Cancer Research.

“The more obese a patient is, the more aggressive the disease,” said Massimo Cristofanilli, MD, associate professor of medicine in the Department of Breast Medical Oncology at The University of Texas M.D. Anderson Cancer Center. “We are learning that the fat tissue may increase inflammation that leads to more aggressive disease.”

Cristofanilli and colleagues observed 606 women with locally advanced breast cancer. These women were classified by body mass index into the following three groups: normal/underweight (24.9 or below), overweight (at least 25 but less than 30) or obese (more than 30). Body mass index is calculated by dividing a person’s weight by their height.

At five years, overall survival was 56.8 percent among obese women, 56.3 percent among overweight women and 67.4 percent among normal weight women. The 10-year survival rate was 42.7 percent among obese women, 41.8 percent among overweight women and 56.5 percent among normal weight women.

The rate of inflammatory breast cancer, previously shown to have worse outcomes than non-inflammatory breast cancer, among obese women was 45 percent compared with 30 percent in overweight women and only 15 percent in women considered normal weight, researchers found.

Risk of breast cancer recurrence was also higher in obese or overweight women. By five years, 50.8 percent of obese women reported a recurrence compared with 38.5 percent of normal weight women. By 10 years, the rate of recurrence was 58 percent among obese women and 45.4 percent among normal weight women.

“Obesity goes far beyond just how a person looks or any physical strain from carrying around extra weight. Particular attention should be paid to our overweight patients,” Cristofanilli said.

Cristofanilli said physicians need to pay close attention to breast cancer patients because commonly used drugs, such as tamoxifen, tend to increase weight gain during treatment.

“We have actually become quite good at managing acute side effects such as nausea in our chemotherapy patients and it goes away within a couple of days,” Cristofanilli said.

“Following the nausea, our patients tend to overeat, which further increases their risk of weight gain. We need to implement lifestyle modifications interventions and develop better methods to follow these patients closely.”

Why tumour cells are herceptin resistant

Sat, 08 Mar 2008 07:47:22 PST

( from http://www.rxpgnews.com ) UC Davis Cancer Center researchers have discovered a likely reason why some tumor cells are inherently resistant — or become resistant over time — to the popular breast cancer drug trastuzumab, commonly referred to by the brand name Herceptin. One in four women with breast cancer are candidates for treatment with Herceptin, which decreases the risk of relapse and prolongs patient survival. For 30 to 50 percent of patients, however, the drug does not work.

"Herceptin revolutionized the treatment of breast cancer," said Colleen Sweeney, associate professor of biochemistry and molecular medicine, co-director of the UC Davis Cancer Center Breast Cancer Research Program and senior author of the study, which is published in the March 1 issue of Cancer Research. "But our clinical experiences indicate that there is room for improvement. We wanted to find out what was reducing Herceptin's effectiveness in some cases."

Introduced in 1998, Herceptin has been used to treat women whose tumor cells test positive for multiple copies of the HER2 gene. Every normal cell carries HER2, which helps cells grow, divide and repair themselves. During cancer development, however, this gene creates extra copies of itself, which helps cancer cells grow and spread. In combination with other medications, Herceptin slows this process by blocking the HER2 cell-growth signal.

Previous research by the UC Davis team showed that another gene called MET could be activated at the same time as HER2, making tumor cells more invasive as a result. For the current study, Sweeney decided to find out if MET also contributes to Herceptin resistance. To do this, the researchers conducted a series of experiments involving three HER2-positive cell lines and 10 HER2-positive primary breast tumors.

They found MET expressed at moderate levels in three HER2 tumor specimens and at high to very high levels in four others. Using one of the cell lines, they showed that MET and HER2 activation together substantially increased tumor-cell proliferation. They went on to show that inhibiting or depleting MET in two HER2 overexpressing cell lines makes HER2-positive breast cancer cells more susceptible to the drug Herceptin, while activating MET reduces the drug's effectiveness. Additional analyses of publicly available microarray data from studies conducted at Yale University showed that MET is overexpressed in Herceptin-resistant tumors.

"The MET gene is waiting in the wings and can take over for HER2 when it is targeted with Herceptin," Sweeney explained. "Some HER2-positive tumor cells express MET and these cells respond to Herceptin by making even more copies of MET. When a woman gets breast cancer, we currently test her tumor for HER2 but don't take MET into account. We believe that looking at just HER2 status is no longer going to tell us the whole story."

Because the proteins encoded by HER2 and MET are both known as receptor tyrosine kinases, or RTKs, Sweeney predicted that breast cancer research will increasingly rely on proteomic as well as genetic testing of tumors that goes beyond HER2 and focuses on finding therapies that target MET and other RTKs expressed in HER2-positive breast cancers. The search is now on for affordable, high-throughput technology that makes possible the complete evaluation of the expression profiles of kinomes, which are families of related RTKs.

"Access to this type of technology will allow us to more rapidly find novel drugs to block the activity of kinomes or even individual kinases and greatly improve the efficacy of existing treatments," she said.

For the next phase of her research, Sweeney will utilize a larger number of patient specimens and attempt to determine whether MET expression predicts Herceptin resistance.

"We need to confirm that the MET receptor is going to be a viable target. If we again find a significant correlation between MET and Herceptin resistance, the next step will be drug studies targeting MET in an animal model," she said.

Which is better-Lapatinib and/or Trastuzumab? International study to answer this

Sat, 01 Mar 2008 03:36:10 PST

( from http://www.rxpgnews.com ) Two targeted medications designed to treat an aggressive form of breast cancer are being tested in a new study involving 8,000 participants in 50 countries across six continents -- a clinical trial that investigators hope will provide a new model for global cancer research. This trial, dubbed ALTTO (Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization study), will be one of the first global initiatives in which two large, academic breast cancer research networks covering different parts of the world have jointly developed a study in which all care and data collection are standardized, regardless of where patients are treated. The networks are The Breast Cancer Intergroup of North America (TBCI), based in the United States, and the Breast International Group (BIG) in Brussels, Belgium. TBCI consists of six National Cancer Institute (NCI)-funded clinical trials cooperative groups. NCI is part of the National Institutes of Health.

ALTTO is designed to answer the most pressing questions regarding use of two widely used cancer agents: whether one agent is more effective, which agent is safer for patients, and what benefit will be derived by taking the drugs separately, in tandem order, or together" The trial is a randomized, Phase III study, which is considered a gold standard method for proving drug effectiveness.

The two agents tested in ALTTO are drugs designed to treat HER2-positive tumors, which is a particularly aggressive form of cancer that affects approximately 20 percent to 25 percent of breast cancer patients. Both agents, trastuzumab (Herceptin) and lapatinib (Tykerb), have already been approved by the U.S. Food and Drug Administration for use for treatment of HER2-positive breast cancer. ALTTO will provide the first head-to-head comparison of trastuzumab and lapatinib in the earliest, most treatable stages of cancer. It will also be one of the first large-scale studies to evaluate lapatinib’s effectiveness in treating early breast cancer.

HER2-positive breast cancer is caused by an excess of HER2 genes or by over-production of its protein, the HER2 cell surface receptor. Trastuzumab consists of large antibodies that once injected into patients, latch on to the portion of the HER2 protein that sits on the outer surface of the cancer cell whereas lapatinib acts by entering a cancer cell and binding to the part of the HER2 protein that lies beneath the surface of the cell.

The trial is unusual in that it has two different designs depending on whether patients with stage I or stage II breast cancer have already been treated with chemotherapy. The study thus will compare four different regimens of targeted therapy administered over a 52-week period. Patients will be randomized to receive either trastuzumab or lapatinib alone, or trastuzumab followed by lapatinib, or the two treatments in combination.

“There have been major improvements in the management of patients with early breast cancer in the last few years, so this new study builds on this knowledge and sets an example of the new era: good science, good worldwide collaboration,” said Edith Perez, M.D., an oncologist in the North Central Cancer Treatment Group (NCCTG) at Mayo Clinic in Jacksonville, Fla., who will lead the study for TBCI. “It may be that using two treatments that work in different ways against HER2-positive breast cancer offers a complementary strategy that is more powerful than either drug alone.”

ALTTO will be one of the first trials of its scope in which translational research -- taking science from bench to bedside -- plays a critical role, investigators say. In ALTTO, biological material will be collected from thousands of patients in order to determine a tumor profile that responds best to the drugs -- information that could lead to individualized patient care and, possibly, to development of next generation agents.

“The difference between this study and many that came before it is that the collection of biological materials occurs as the trial is being conducted, not as an afterthought. While there are exceptions, not many companies or organizations have been willing to invest in that kind of research before,” said Martine J. Piccart, M.D., Ph.D., professor of oncology at the Université Libre de Bruxelles, Belgium, and lead investigator for BIG, which she founded in 1996. “Now we have the chance to optimize therapy with powerful drugs in order to provide the best treatment possible for each of our patients.”

Perez and Piccart led the development team of the ALTTO trial and will act as the study’s co-principal investigators. On behalf of BIG and TBCI, these two lead investigators have been working toward collaborative clinical studies for a number of years. The ALTTO study, they say, represents a new paradigm that blends the high standards of both systems in order to test the latest breast cancer treatments as efficiently as possible in thousands of women worldwide.

"The NCI greatly appreciates the work that Mayo Clinic, TBCI and BIG are doing to help advance our understanding of the complex mechanisms that underlie different types of breast cancer,” said Jo Anne Zujewski, M.D., a senior investigator in the clinical investigations branch at NCI. “We hope that this model of international collaboration is one which we can build upon in the future."

Lapatinib, in combination with the chemotherapy drug capecitabine, was approved by the U.S. Food and Drug Administration in March 2007 for the treatment of advanced or metastatic HER2-positive breast cancer in patients who had received prior therapy with three agents -- an anthracycline, a taxane and Herceptin. GlaxoSmithKline is providing the study drug, as well as additional financial support for the ALTTO trial. All drugs carry potential side effects, and more information of side effects for lapatinib and trastuzumab can be found in the Q&A at http://www.cancer.gov/newscenter/pressreleases/ALTTOQandA. NCI and GSK also provided comment and input on the design of the study.

NCCTG will act as the treatment base for ALTTO in North America. BIG is a network of 41 non-U.S. research groups from around the world. Its Brussels-based BrEAST Data Center is providing centralized data management for the global study (including the United States). The other members of TBCI include the Eastern Cooperative Oncology Group (ECOG), the Cancer and Leukemia Group B (CALGB), the Southwest Oncology Group (SWOG), the American College of Surgeons Oncology Group (ACOSOG), and the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG).

To date, more than 300 centers around the world have enrolled patients into ALTTO. Full enrollment is expected to involve about 500 centers in the United States and more than 800 centers in Europe and the rest of the world. A complete listing of ALTTO participating sites can be found by searching for ALTTO at http://clinicaltrials.gov.

Breast cancer diagnosis comes late for women in gentrifying neighborhoods

Tue, 05 Feb 2008 23:29:37 PST

( from http://www.rxpgnews.com ) Women who live in Chicago's gentrifying neighborhoods are more apt to receive a late diagnosis of breast cancer than women who live in poverty-stricken neighborhoods, University of Illinois at Chicago researchers have found.

The surprising finding is in a study published in the January issue of the Annals of Epidemiology.

There's been a lot of social change in American cities since 1990, but we know very little about how gentrification impacts health outcomes, said Richard Barrett, researcher at the UIC Institute for Health Research and Policy and lead author of the study. We know that minority women in Cook County are more likely to be diagnosed with late-stage breast cancer and to die from it compared with white women, but we were interested in how neighborhood change impacts breast cancer diagnosis.

Previous research indicated that places with more people of higher socioeconomic status tend to have lower rates of distant metastasis when diagnosed with breast cancer, Barrett said.

That would lead one to assume that if an area becomes gentrified, then the proportion of breast cancer cases diagnosed with distant metastases would decline, and patients should have a better chance for survival.

Our study showed that is not true.

The researchers analyzed Illinois State Cancer Registry data in
conjunction with Cook County census tract data. The cancer data included
information on age, race, ethnicity and stage at diagnosis for 21,516
breast cancer cases between 1994 and 2000 among women living in Cook County.

Chicago is a great laboratory to study racial and ethnic disparities in
health, and how your neighborhood can affect your health, said Barrett, who is an associate professor of sociology at UIC.

To measure neighborhood change between 1990 and 2000, the researchers
tracked changes in owner-occupied housing values, professional and managerial employment, and adults with a college education.

The researchers found that women living in neighborhoods with concentrated disadvantage, concentrated levels of immigration, and lower levels of affluence in 1990 ran a greater risk of distant-stage diagnosis of breast cancer. Yet when some of these neighborhoods gentrified, women there ran a higher risk of distant-stage metastasis of breast cancer than did women living in similar neighborhoods that did not gentrify.

The UIC researchers suggest that women living in upward-changing neighborhoods may experience disruption of social networks, interruption in access to health care services, and stress relating to social isolation and financial problems as housing costs rise.

Fighting resistance to tamoxifen- breakthrough in breast cancer treatment

Sun, 20 Jan 2008 09:17:28 PST

( from http://www.rxpgnews.com ) Researchers at the Tenovus Centre for Cancer Research at Cardiff University have made a breakthrough in breast cancer treatment that could help save the lives of women who become resistant to breast cancer drugs such as tamoxifen.

While drugs such as tamoxifen have been a huge success in treating breast cancer, for a significant proportion of sufferers the drugs either fail to work, or after an initial successful response the patient relapses as the cancer acquires or possesses resistance to the drug.

However the researchers have discovered that inhibiting the activity of a certain protein in the cancer could prevent or even reverse the resistance to tamoxifen. The researchers noticed that when breast cancer cells grown in the laboratory develop resistance to tamoxifen, they show a large increase in the activity of a protein known as Src – and by stopping this activity resistance to tamoxifen can be prevented and even reversed.

Dr Stephen Hiscox of the Welsh School of Pharmacy, who led the research team and has just been appointed as one of the Cancer Research UK Cardiff University Research Fellows explained: “We have previously shown that when breast cancer cells become resistant to medicines such as tamoxifen in the laboratory they become more aggressive with an invasive behaviour. These are characteristics that can be promoted by Src, a protein which we have recently shown to be more active in tamoxifen-resistant than tamoxifen-sensitive breast cancer cells.

“As part of collaborative research between Tenovus and AstraZeneca, it was found that this aggressive, invasive behaviour could be reduced by treating the cells with a specific inhibitor of Src activity, AZD0530. Surprisingly, AZD0530 also made the tamoxifen-resistant cells sensitive to tamoxifen again. In addition, we found that co-treating the cells with a combination of tamoxifen and AZD0530 could actually prevent drug resistance occurring in the first place.”

The Src inhibitor AZD0530 developed by AstraZeneca is currently in early clinical trials. If the results seen in the laboratory can be reproduced in the clinic, this approach could offer a substantial clinical benefit to a large number of women with breast cancer, as Professor Robert Nicholson, Director of the Tenovus Centre for Cancer Research, explains:

“Whilst little is known about the mechanisms used by breast cancers to become resistant to common therapies such as tamoxifen, it remains a significant clinical problem. Therefore the ability to restore sensitivity to therapy, or to even prevent resistance arising in the first place, could be of huge benefit to a large number of breast cancer patients.”

Lapatinib (Tykerb) and capecitabine (Xeloda) shrink breast cancer metastases in the brain

Sun, 16 Dec 2007 09:57:20 PST

( from http://www.rxpgnews.com ) A combination of a "targeted" therapy and chemotherapy shrank metastatic brain tumors by at least 50 percent in one-fifth of patients with aggressive HER2-positive breast cancer, according to data presented by Dana-Farber Cancer Institute investigators at the San Antonio Breast Cancer Symposium.

Lapatinib (Tykerb) and capecitabine (Xeloda) were paired in an extension of a Phase 2 clinical trial in which lapatinib given alone shrank brain metastases significantly in six percent of 241 patients.

In the extension trial, capecitabine was added to lapatinib in 49 patients whose metastases -- cancerous colonies in the brain spread from their primary cancer -- had progressed while on treatment. With the combination therapy, brain metastases shrank by 20 percent or more in 18 patients (37 percent) and shrank by at least 50 percent in 10 patients (20 percent), reported Nancy Lin, MD, of Dana-Farber's Breast Oncology Center.

"Very few medications have shown activity in the treatment of brain metastases, particularly in HER-2-positive metastatic breast cancer patients," said Lin, who led the study with Eric Winer, MD, director of the Dana-Farber Breast Oncology Center. "Therefore, these data are quite encouraging, and further studies are warranted."

The data (abstract 6076) will be presented on Sunday, Dec. 16 at 7 a.m. CT.

Lapatinib is an oral small-molecule drug from GlaxoSmithKline that is approved along with capecitabine for treating patients with advanced or metastatic breast cancer whose tumors are driven by the abnormal growth signal, HER-2, and who have already undergone therapy including trastuzumab (Herceptin), a taxane drug, and an anthracycline compound. Lapatinib, like trastuzumab, blocks the HER-2 signal.

Up to one-third of women with advanced, HER-2-positive breast cancer may develop metastases to the brain.

"Although radiation treatment is often effective, as women live longer with metastatic cancer, some develop worsening of brain metastases despite radiation," said Lin. "Because cancer in the brain can have a major impact on quality of life, it is important to have treatment options to address this problem."

Osteoporosis drug approved to cut breast cancer risk

Sat, 15 Sep 2007 13:39:25 PST

( from http://www.rxpgnews.com ) In 1997, FDA approved Evista, which is manufactured by Eli Lilly and Company, for the prevention of osteoporosis in postmenopausal women and in 1999, for the treatment of osteoporosis in postmenopausal women.

Evista Friday became the second drug approved to reduce the risk of breast cancer. Evista is commonly referred to as a selective oestrogen receptor modulator -. In reducing the risk of invasive breast cancer, SERMs may act by blocking oestrogen receptors in the breast.

'Today's action provides an important new option for women at heightened risk of breast cancer,' Steven Galson, director of FDA's Centre for Drug Evaluation and Research, said Friday.

'Because Evista can cause serious side effects, the benefits and risks of taking Evista should be carefully evaluated for each individual woman,' he said.

The serious side effects include blood clots in the legs and lungs, and death due to stroke. Women with current or prior blood clots in the legs, lungs, or eyes should not take Evista. Other potential side effects include hot flashes, leg cramps, swelling of the legs and feet, flu-like symptoms, joint pain, and sweating.

Evista should not be taken by pre-menopausal women and women who are or may become pregnant because it may cause harm to the unborn baby, FDA warned in its statement.

In addition, Evista should not be taken with cholestyramine - or estrogens.

Evista does not completely prevent breast cancer. Breast examinations and mammograms should be done before starting Evista and regularly thereafter, said FDA.

Study finds new link between estrogen and breast cancer

Fri, 24 Aug 2007 03:36:37 PST

( from http://www.rxpgnews.com ) The female sex hormone estrogen turns on a gene linked to breast cancer, according to new research by Brisbane scientists.

The cancer biology team from UQ's Diamantina Institute for Cancer, Immunology and Metabolic Medicine, believe their finding will help explain the link between breast cancer and high levels of estrogen.

?What we've shown is that the ability of estrogen to switch this gene on is important for the growth of breast cancer cells,? Diamantina cancer biology research leader Professor Tom Gonda said.

The gene they studied, known as MYB, is found in about 70 percent of all breast cancers and is one of several dozen genes called oncogenes that promote cancer growth.

?What's important in breast cancer is the ability of estrogen to turn on MYB rather than there being a mutation in the gene itself,? Professor Gonda said.

He said the next step was to take the results, which come from isolated cancer cells grown in the laboratory, and test them in laboratory mice that are a better model for human patients.

?We're trying to show directly that MYB can induce cancerous changes in normal breast cells.?

Professor Gonda and his colleagues at UQ worked with researchers in Melbourne, Adelaide and the United States and published their findings this month in the prestigious scientific journal Proceedings of the National Academy of Sciences of the USA.

He said a drug that blocks the action of MYB might be used to treat breast cancer in the future but he warned that would take many years of hard work.

Support groups don't extend survival of metastatic breast cancer patients, Stanford study finds

Mon, 23 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) A new study from a team of Stanford University School of Medicine researchers led by David Spiegel, MD, shows that participating in support groups doesn't extend the lives of women with metastatic breast cancer. The results differ from oft-cited previous findings by Spiegel that showed group psychotherapy extended survival time.

The newest research did, however, confirm that support groups improved quality of life for the participants, and showed a survival benefit for a subgroup of patients with an aggressive form of breast cancer.

We didn't confirm earlier observations that group psychotherapy extends overall survival for women with metastatic breast cancer, but we did again show a positive effect on mood and pain, said Spiegel, professor and associate chair of psychiatry and behavioral sciences. I still very much believe this type of therapy is crucial to cancer care.

The paper will be published in the Sept. 1 issue of CANCER, the journal of the American Cancer Society, and will appear in the online version of the journal on July 23.

Spiegel is well-known for his work on support groups for cancer patients. His studies and others have previously shown the groups can lead to better coping, improved mood, and reduced pain, depression and anxiety for cancer patients. When Spiegel started his research in the 1970s, virtually no cancer patients were in support groups, he said, but now the therapy is a much more accepted part of cancer care.

Almost every cancer center, including Stanford's, offers some sort of support group, he pointed out.

In 1989, Spiegel garnered the attention of oncologists and others when he published a study in the journal The Lancet showing dramatic benefits of support groups. His study of 86 metastatic breast cancer patients found those women who were randomly assigned to attend support groups for one year experienced less depression and pain and also wound up living 18 months longer (37 vs. 19 months) than those who weren't. We were shocked when we saw the magnitude of the effect, Spiegel told the New York Times that year.

In the years since, numerous researchers have attempted to replicate Spiegel's findings, with mixed results. According to Spiegel, four other published trials found that the therapy produced both psychological and survival benefits; this includes a recently published Journal of Clinical Oncology study with a 10-year follow-up. Six published studies, including a 2001 New England Journal of Medicine study involving 235 metastatic breast cancer patients, found that group therapy helped improve quality of life but did not lengthen survival.

Spiegel launched the latest prospective study in 1991, tracking 125 metastatic breast cancer patients for periods of up to 10 years in an effort to replicate his original findings. The women, whose cancers were comparable in type and prognosis, were randomly assigned to either group support, psychotherapy and educational materials, or to educational materials alone. The 64 women assigned to group support met for 90 minutes once a week for at least one year; some participated for as long as 10 years. Spiegel recalls one participant remarking, This group is the least superficial thing I do in my life.

After tracking the women for more than a decade, Spiegel and his colleagues found an improvement in the therapy participants' level of distress, anxiety and pain. They did not, however, find a difference in overall survival between those women who attended therapy and those who didn't. The women who attended group therapy had a median survival of 31 months, and the group that received education materials alone survived a median of 33 months.

The big question was whether there was an overall survival advantage for those people in therapy, and the answer was no, said Spiegel. I was surprised and a little disappointed by the findings.

One possibility for the difference between his earlier study and this one, Spiegel said, is that both the medical treatments and the emotional climate for breast cancer patients have improved dramatically, making it more likely for patients to live longer even without the benefit of psychotherapy.

Spiegel notes that he and his colleagues did find psychotherapy benefited women with estrogen receptive-negative tumors, an aggressive type of breast cancer that fails to respond to the newest hormonal treatments. These women - who comprised 20 percent of the study group - had a median survival of almost 30 months, which was 21 months longer than those who received educational literature alone.

Had we not found this sub-group effect, I might have said we're done doing research in this area, said Spiegel. But this finding looks really interesting, and it's something to continue studying.

Spiegel said that despite the overall findings on survival, it remains very clear that support groups provide great benefits to cancer patients and should be an important part of treatment. I've never told my patients to join a support group because it makes you live longer - I've said to do it because it helps you to live better, he said.

Electromagnetic breast imaging techniques offer high contrast and ability to distinguish between healthy breast tissue and abnormal tissue

Wed, 06 Jun 2007 16:01:37 PST

( from http://www.rxpgnews.com ) Dartmouth physicians and engineers have published a paper with results from a five-year project testing three new imaging techniques to examine breast abnormalities, including cancer. The study finds that the new methods of electromagnetic imaging offer a high contrast and the ability to distinguish between healthy breast tissue and abnormal tissue. Their study appears in the May 2007 issue of Radiology, the journal of the Radiological Society of North America.

The interdisciplinary team includes researchers from Dartmouth's Thayer School of Engineering and Dartmouth Medical School working with experts at the Norris Cotton Cancer Center and the Department of Radiology at Dartmouth-Hitchcock Medical Center (DHMC). The electromagnetic techniques are electrical impedance spectral imaging (EIS), microwave imaging spectroscopy (MIS), and near infrared (NIR) spectral imaging.

A total of 150 women participated in this study, 97 of whom had an abnormal conventional breast image that was suspicious or highly suggestive of malignancy and were scheduled for a biopsy. The women with abnormal breast images underwent electromagnetic exams prior to biopsy. The researchers compared the abnormal area with the background breast tissue and with a mirror image area in the opposite breast and correlated the data with the biopsy findings. Further analysis led the researchers to determine that the new imaging techniques provided an increase in contrast between 150 to 200 percent to discriminate between breast cancer and benign tissue.

?We put our new imaging techniques to the test to quantify their effectiveness,? said Steven Poplack, associate professor of radiology and OB/GYN at Dartmouth Medical School, and co-director for breast imaging/mammography at DHMC, and the lead author of the paper. ?Our results show the potential power of using a variety of imaging techniques to get the best possible view of what?s going on in the breast tissue.?

Specifically, the three techniques demonstrated significant differences in region-of-interest image summaries of normal versus abnormal breasts for EIS, across diagnostic groups for NIR, and for MIS when analysis was restricted to lesions larger than one centimeter. The electromagnetic imaging modalities appeared even more accurate when all are used in concert.

EIS: This painless test uses a very low voltage electrode system to examine how the breast tissue conducts and stores electricity. Living cell membranes carry an electric potential that affect the way a current flows, and different cancer cells have different electrical characteristics.

MIS: This exam involves the propagation of very low levels (1,000 times less than a cell phone) of microwave energy through breast tissue to measure electrical properties. This technique is particularly sensitive to water. Generally, tumors have been found to have more water and blood than regular tissue.

NIR: Infrared light is sensitive to blood, so by sending infrared light through breast tissue with a fiber optic array, the researchers are able to locate and quantify regions of oxygenated and deoxygenated hemoglobin. This might help detect early tumor growth and characterize the stage of a tumor by learning about its vascular makeup.

Study finds difference in survival rates among white and black women with advanced breast cancer

Wed, 06 Jun 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Despite modest overall improvements in breast cancer survival rates for women with advanced disease over the last two decades, the rates for black women have not improved and the difference in life expectancy between white and black women continues to widen, according to researchers at The University of Texas M. D. Anderson Cancer Center.

The study, presented today (June 3) at the 43rd annual American Society of Clinical Oncology (ASCO), is the first to show that improvements in breast cancer survival only benefit white women and that the disparity between black and white breast cancer patients is widening.

The study evolved as a follow-up to recent research of Sharon Giordano, M.D., assistant professor in M. D. Anderson's Department of Breast Medical Oncology, that found an overall improvement in the survival of Stage IV breast cancer patients enrolled in clinical trials at M. D. Anderson.

We wanted to expand our research and look to a bigger subset of patients treated in the community to see if we would find similar results, says Shaheena Dawood, M.D., a Susan G. Komen Fellow in Breast Medical Oncology at M. D. Anderson. We thought we would find that there was improvement in women with Stage IV breast cancer regardless if patients were white or black, with white women likely having better outcomes. Rather, over the decades, we found that black women's survival did not improve at all.

The researchers analyzed the National Cancer Institute's Surveillance Epidemiology and End Results (SEER) database to identify 15,438 women who were newly diagnosed with advanced breast cancer between 1988 and 2003. Adjustment factors included: patient age; estrogen receptor status; and tumor grade.

Patients were divided into three subgroups: those diagnosed from1988 to 1993; from 1994 to 1998; and from 1999 to 2003. Overall, the median age of the women was 62 years old; median breast cancer-specific survival was 20 months, 21 months and 25 months respectively.

In those diagnosed with advanced breast cancer between 1988 and 1993, the median survival was 20 months in white women, compared to 17 months for black women, a one-year survival difference of 2.8 percent. In the women diagnosed between 1994 and 1998, a white breast cancer patient's median survival was 22 months versus 16 months in black patients, a one-year survival difference of 6.8 percent. In those diagnosed from 1999 to 2003, the median survival for white women was 27 months compared to 17 months for black women, a one-year survivor difference of 8.8 percent.

We do not suspect that these statistics are due to the biology of the disease because we would not expect the biology to change over time. It's more likely due to socio-economic factors, says Giordano, the study's senior author. While SEER data does not code for treatment, we hypothesize that lack of access to healthcare and to newer modalities for treatment of Stage IV breast cancer, such as targeted therapies like Herceptin and aromotase inhibitors, are two contributing factors for the growing disparity.

In 2007, more than 180,510 women will be diagnosed with breast cancer and approximately 40,910 women are expected to die from the disease, according to the American Cancer Society. Of the new cases of breast cancer, the researchers say that 10 percent of the patients are diagnosed with metastatic breast cancer and that mortality rates for women with advanced breast disease are decreasing by 2.3 percent annually.

The researchers hope that health policy makers take notice of the growing disparity and implement steps to make all breast cancer treatments more accessible. Giordano and Dawood also intend to expand upon their research and determine the causation of these racial disparities.

HRT Decline Reduced Breast Cancer Incidence

Thu, 19 Apr 2007 11:12:55 PST

( from http://www.rxpgnews.com ) An extended analysis of cancer rates reinforces a strong association between use of hormone replacement therapy (HRT) and increased breast cancer incidence, according to new research. The decline occurred primarily in women age 50-69, the researchers find, and was predominantly seen in estrogen-receptor(ER)-positive cancer - the type of tumors is fueled by estrogen, a hormone that is supplemented in HRT. Such cancers declined 14.7 percent in this time period, compared to a non-significant decline of 1.7 percent in ER-negative tumors.

"For our new data set, 2004, the drop in breast cancer incidence leveled off and remained low in that year, "showing that the decreased rates seen in 2003 were also present in 2004, meaning that the decline was not a one-year wonder, a short-lived anomaly," says Ravdin, the study's lead investigator.

"This kind of study can't prove causality, but the data present a very compelling link between hormone replacement therapy and breast cancer," says Berry, the study's senior investigator.

Using data derived from National Cancer Institute (NCI) cancer registries that report on 9 percent of the U.S. population, they found that the total decrease in breast cancer incidence was 6.7 percent between 2002 and 2003. They also calculated that by the end of 2002, about 20 million fewer prescriptions for HRT were written in the United States- a decrease of 38 percent. Interest in HRT use dropped after the 16,608-participant federal Women's Health Initiative study results were announced in July 2002 and showed that the risks of taking these agents outweighed the benefits for many post-menopausal women.

Ravdin and Berry strongly stress, however, that their study is not suggesting that all women stop their use of HRT.

"This study is not saying that an individual woman will reduce her absolute risk of developing breast cancer by 15 percent by immediately discontinuing use of HRT," Berry says.

While it may be true that stopping use of HRT may have prevented as many as 14,000 breast cancers in 2003 compared with 2002, the percentage of decline is based on an entire population, he explains. "At best, based on this analysis, an individual woman could reduce her individual risk of developing breast cancer by one in 60, or about 1.7 percent, if she stopped using hormones," Berry says.

As a physician, Ravdin tells his patients to follow currently accepted guidelines for HRT use: to use the drug at the lowest dose and for the shortest time period to control hot flashes and other debilitating symptoms caused by the onset of menopause.

"The risk of developing breast cancer from use of these hormones is relatively small and for some women with postmenopausal symptoms, the benefits of HRT are well worth that risk," he says. "This is just another small piece of the puzzle to help women gauge the risks and benefits of using HRT."

The researchers also say that their study cannot answer three key questions: whether stopping the use of HRT leads to a permanent or a temporary decline in breast cancer incidence; if this effect is seen for stopping all types of HRT; and how much of a contributing role other factors may have played in the decline.

"There are several possibilities as to what effect stopping HRT has. Possibly, it slows the growth of tumors that are there but aren't big enough yet to be detected on a mammogram. Or it could be removing the hormone fuel stops the growth completely or even causes tumor regression," Berry says. "We don't know which is correct."

While Berry, an expert in statistics, adds that he was initially surprised that stopping HRT use could have such an immediate impact on breast cancer growth, Ravdin, the clinician, says he was not.

"We know that if you treat ER-positive breast cancer with anti-hormone treatment, you can see shrinkage within weeks, so why wouldn't withdrawing hormones have the same kind of effect on smaller cancers that have not yet been detected?" says Ravdin. "My thought is that these tumors don't completely disappear, but they have stopped growing - hopefully, for many of them, forever."

As to the impact of other factors on breast cancer decline, the researchers say that one contributing factor could be declining use of mammography by women who have stopped using HRT. NCI data has reported a 3.2 percent decline in screening mammography in 2003 for women 50-65 years old, compared to 2000, Berry says, but adds, "such a change would seem insufficient to explain the decline in breast cancer incidence." A large drop in screening would have been seen in breast tumors that are both ER-positive and ER-negative, and that wasn't the case.

Finally, the researchers say that this study may lead to new insights into both the etiology of breast cancer and its prevention. "We will continue modeling incidence rates to try to understand whether what we are seeing is a slowing or a regressing of tumors, or a mix between these two things," Berry says.

The study was funded by grants from the National Cancer Institute and from M. D. Anderson. Co-authors also include Kathy Cronin, Ph.D., Nadia Howlander, M.S., Christine Berg, M.D., Eric Feuer, Ph.D., and Brenda Edwards, Ph.D., from the National Cancer Institute, and Rowan Chlebowski, M.D., Ph.D., from Harbor UCLA Medical Center. 04/18/07

Should all women in 40s be routinely screened for breast cancer?

Thu, 05 Apr 2007 11:51:27 PST

( from http://www.rxpgnews.com ) Should all women in their 40s be routinely screened for breast cancer? Not necessarily, according to the American College of Physicians. In a new set of guidelines for clinicians of 40-something patients, the group recommends that mammography screening decisions be made on a case-by-case basis. It advises clinicians to discuss the benefits and harms of screening with the patient, as well as each woman's individual cancer risk and preference about screening.

The organization based its recommendations, which will be published in the April 3 issue of Annals of Internal Medicine, on a rigorous review of evidence showing there is variation in the benefits and harms associated with mammography among women in their 40s. The American College of Physicians is the leading professional organization for internal medicine specialists, with a membership of 120,000.

"There are important benefits to screening mammography, but we believe the decision to be screened should be based on an informed conversation between a patient and her physician," said health policy expert Douglas K. Owens, MD, MS, a researcher with the Veterans Affairs Palo Alto Health Care System and a professor of medicine at the Stanford University School of Medicine, who chaired the committee that developed the guidelines. "In our view, the evidence doesn't support a blanket recommendation for women in this age group."

Breast cancer is the second-leading cause of cancer related death among women in the United States; according to the American Cancer Society, 25 percent of all diagnosed cases are among women younger than age 50. Among these younger women, the risk of breast cancer varies greatly - from less than 1 percent for a 40-year-old woman with no risk factors to 6 percent for a 49-year-old woman with multiple risk factors, which include family history of breast cancer, older age at the birth of her first child and younger age at the onset of menstruation.

Physicians and medical groups have for years debated the merits of screening mammography for women in their 40s. While it is well-established that mammography reduces mortality from breast cancer in 50- to 70-year-old women - and that women in this age-group should be routinely screened - the evidence isn't as clear-cut for younger women.

Five years ago, the U.S. Preventive Services Task Force, an independent panel of experts in primary care and prevention, examined data from numerous clinical trials and estimated that screening mammography every one or two years in women in their 40s resulted in a 15 percent decrease in breast cancer mortality after 14 years of follow-up. But a separate Canadian study published in the same issue of the journal found that women in this age-group received no benefit from mammography.

Past analyses have also made note of the potential harms of screening, including radiation exposure, procedure-associated pain, false-positive results, over-diagnosis and potentially unnecessary treatment.

Based in part on the conflicting evidence, medical groups have differing screening recommendations for women under age 50. The U.S. Preventive Services Task Force and the American College of Obstetricians and Gynecologists both recommend screening mammography every one to two years for women in their 40s, while the 2006 American Cancer Society guideline recommends yearly mammograms starting at age 40.

Because of the ongoing controversy, the American College of Physicians' Clinical Efficacy Assessment Subcommittee decided to take its own look at the evidence related to screening in women in their 40s. After their review, the group concluded that screening mammography for women in this age group likely provides a modest reduction in breast cancer mortality, but - as with any screening intervention - it also comes with the risk of potential harms.

In the new guidelines, the organization emphasizes the importance of using a woman's concerns about breast cancer and screening to help guide decision-making about mammography. Women's thoughts about mammography or their risks of developing breast cancer will likely vary greatly, the group notes, but it expects the potential reduction in breast cancer mortality associated with screening to outweigh other considerations for many women.

"We still think many women will choose to get mammography, and we're supportive of that," said Owens. "The most important thing is that women be well-informed about the decision they're making."

Computerized reminders boost mammography screening rates

Thu, 05 Apr 2007 11:46:15 PST

( from http://www.rxpgnews.com ) Findings of a new Mayo Clinic study published this week in Archives of Internal Medicine show that a computerized mail and phone reminder program can significantly increase the percentage of patients receiving preventive health services and improve the value of health care.

"National evidence-based guidelines say every woman over age 40 should have a yearly mammogram, but only about 65 percent of women nationally have had one in the last two years," explains Rajeev Chaudhry, M.B.B.S., the Mayo Clinic physician who led the study. "In this study we showed we can increase that percentage through a team approach, and we're applying the findings to other chronic disease and preventive services, too."

The researchers divided a population of 6,675 women aged 40â75 into two nearly equal groups: one to get mailings and, if necessary, a phone call to remind them to schedule a mammogram; and a control group that did not receive reminders. Among the reminded group, 64.3 percent had their yearly mammogram, compared to 55.3 percent in the control group. As the program has expanded following the study period, compliance with yearly mammograms has now grown to over 72 percent, with 86 percent having had one within the previous two years.

Dr. Chaudhry said a redesign of the primary care practice to enable appointment secretaries to schedule preventive services was a key to the program's success.

"In the old way, a woman had to remember that it was time for her yearly mammogram and call her physician's appointment secretary, who then got the doctor's approval for the test," he explains. "Then the secretary had to get back in touch with the woman to schedule the mammogram. That made the process more complicated, time-consuming and expensive than it needs to be, with several places where missed communication could mean the test didn't get done. With our new electronic tool and our related practice changes, one appointment secretary can now schedule mammography for over 10,000 women. When women get the reminder notice, it means they are preapproved, so the mammography can be scheduled with the first phone call without having to consult the physician."

"Not everyone needs to see a doctor every year, but they still should get the appropriate preventive care and screenings," explains Robert Stroebel, M.D., chair, Division of Primary Care Internal Medicine at Mayo Clinic and the study's senior author. "We were pleasantly surprised at how much we could increase mammography percentages through this new system. As we get more women screened, we're also going to find cancers earlier, when we're more likely to be able to treat them successfully. The goal is to improve the value of heath care, providing higher quality at lower cost by having all members of the health care team working at their highest potential," Dr. Stroebel says. "We already have expanded this reminder method to Pap smears and diabetes care, and will be adding other preventive services this year."

"This kind of practice happens in other fields," says co-author Rosa Cabanela. "Dentist practices, for example, typically call or mail patients to remind them to make an appointment. Health care has been behind many other industries in using technology to optimize service and efficiency. It's time to catch up."

Dr. Chaudhry says the study has important implications in designing better care delivery systems. "With baby boomers getting older and having more chronic conditions, it's estimated that a primary care physician may have to spend up to six hours a day managing the preventive services and chronic disease tests for his or her patient population," he says. "By using information technology and a team approach to manage chronic and preventive care, we can free physicians to focus on the individualized needs of their patients."

Recent declines in breast cancer mortality most significant in women under 70

Tue, 03 Apr 2007 03:03:33 PST

( from http://www.rxpgnews.com ) A new study shows that recent declines in breast cancer mortality rates have been most significant among women with estrogen receptor (ER)-positive tumors and women younger than 70. The results of the study are being published online April 2 in the Journal of Clinical Oncology (JCO).

Approximately 75% of breast cancers are ER-positive. The average age of breast cancer diagnosis is 62.

Between 1990 and 2003, breast cancer mortality rates declined by 24%. This is the first study to examine which patients have experienced the greatest declines in mortality. In 1989, the mortality rate for breast cancer peaked at 33 out of 100,000 women per year. By 2003, the mortality rate had dropped to 25 out of 100,000 women per year.

Although breast cancer mortality has declined for all groups of patients, declines were greatest for women under 70 and women whose tumors were ER-positive. The researchers found that among women under 70, mortality from breast cancer declined 38% for those with ER-positive tumors vs. 19% for those with ER-negative tumors. Among women 70 or older, mortality declined 14% for those with ER-positive tumors vs. no decline for those with ER-negative tumors.

'These trends in breast cancer mortality since 1990 are likely attributable to at least two important factors: the use of tamoxifen after surgery, which substantially reduces the risk of recurrence in ER-positive tumors only; and widespread use of screening mammography, which is more likely to detect the slow-growing tumors that tend to be ER-positive,' said Ismail Jatoi, MD, PhD, Director of the Breast Cancer Center in the Department of Surgery at the National Naval Medical Center, and the study's lead author.

This study did not explore the reasons why breast cancer mortality rates declined less for older women. However, previous studies have suggested that older women are less likely to receive adjuvant therapy for breast cancer. Because older women are under-represented in clinical trials, their optimal treatment has not been well established.

The researchers point to the importance of further reducing mortality rates among women over 70 and women with ER-negative tumors. The authors argue that recruiting more older women into clinical trials could lead to better treatments and outcomes for this age group. In addition, while a number of breast cancer drugs have recently been introduced that are likely to benefit women with ER-negative tumors, any impact they would have on mortality was not seen during this study period. For example, adjuvant use of Herceptin (trastuzumab) was approved in November 2006 for HER-2+ breast cancer (many ER-negative breast cancers are HER2+).

Investigators at the National Cancer Institute (NCI) and the National Naval Medical Center looked at 234,828 cases of invasive female breast cancer diagnosed between 1990 and 2003. The study analyzed data from the Surveillance Epidemiology and End Results (SEER) cancer registry, an NCI-sponsored, population-based database that compiles detailed cancer statistics.

Older women with breast cancer get a lower level of care than younger women

Fri, 30 Mar 2007 01:55:55 PST

( from http://www.rxpgnews.com ) Compared to younger women, older women with breast cancer are less likely to be diagnosed via needle biopsy and triple assessment, less likely to undergo surgery and less likely to receive radiotherapy, the researchers report in this week's British Journal of Cancer.

Such management of older women is likely to lead to higher rates of local recurrence of the disease and higher than necessary mortality. Dr Katrina Lavelle, who led the study at the University's School of Nursing, Midwifery and Social Work, explains: "We have found that older women from aged 70 and over are less likely to receive the same breast cancer care as younger women and that this is related to their age rather than differences in the biology of their tumour."

The highest incidence of breast cancer in England occurs in women aged 70 years and older. Older women also experience the worst survival - women aged 70-79 have a 76% five-year relative survival compared to 80% for all ages, and for women aged 80 plus this drops considerably to 61%, beyond what might be expected owing to an increase in age.

The team carried out a retrospective cohort study involving case note review based on the North Western Cancer Registry database of women aged 65 and over, resident in Greater Manchester with invasive breast cancer registered over a one year period. The results of the study, funded by an NHS R&D Training Fellowship, may be generalized nationally as variation in survival between regions is lower for breast cancer compared to other cancers.

The they found that, compared to women aged 65-69 years, women aged 80 plus with operable breast cancer have increased odds of not receiving triple assessment, not receiving primary surgery, not undergoing axillary node surgery and not undergoing steroid receptor tests (which indicate suitability for hormone therapy). Compared with her 65-69-year-old counterpart, the odds of a woman aged 80 or older not receiving triple assessment for operable breast cancer are five-and-a-half times higher, and the odds of her not receiving surgery are more than 40 times higher. Even women as young as 70-74 have over 7 times the odds of not receiving radiotherapy following breast conservation surgery compared to women aged 65-69 years.

In addition, the team discovered that the overall percentage of women in all the age groups not receiving steroid receptor tests was high at 41%, which resulted in treatment decisions being taken without this fundamental information. Three quarters of the patients who did not receive steroid receptor tests were given the hormone therapy, tamoxifen: that is, prescribed a treatment without evidence that it would work.

In a survey of UK breast cancer surgeons in 2004, 75% reported that they would treat older breast cancer patients in a similar way to younger patients and 98% responded that the cut off point for breast cancer surgery was not age related. Dr Lavelle says: "Clearly there is a difference in clinicians' perceptions of how older breast cancer patients should be treated and their actual practice.

"Standard management of breast cancer was infrequent in older women in Greater Manchester. The lack of diagnostic and steroid receptor testing resulted in older cancer patients having no effective treatment with 41% not undergoing a steroid receptor test, 32% of whom received tamoxifen as their sole form of treatment. "Mortality of elderly breast cancer patients is unlikely to improve where this pattern of management persists."

Research lead for the School of Nursing, Midwifery and Social Work, Professor Chris Todd, commented: "It would be wrong to conclude that ageism is to be found in the NHS on the basis of these results alone, as this study has not been able to take the preferences of older women themselves into account. This is something we intend to investigate in the next phase of our research.

UBC discovery may lead to focussed therapies for metastatic breast, ovarian cancer

Mon, 19 Mar 2007 23:01:33 PST

( from http://www.rxpgnews.com ) New non-toxic and targeted therapies for metastatic breast and ovarian cancers may now be possible, thanks to a discovery by a team of researchers at the University of British Columbia.

In a collaboration between UBC stem cell and cancer scientists, it was found that a protein called podocalyxin â which the researchers had previously shown to be a predictor of metastatic breast cancer â changes the shape and adhesive quality of tumour cells, affecting their ability to grow and metastasize. Metastatic cancer is invasive cancer that spreads from the original site to other sites in the body.

The discovery demonstrated that the protein not only predicted the spread of breast cancer cells, it likely helped to cause it. The findings were recently published online by the Public Library of Science.

"We believe weâve found a new important culprit in metastatic breast cancer, which opens up an entirely new avenue of cancer research," says Calvin Roskelley, an associate professor of cellular and physiological science who specializes in breast cancer and is co-senior principal investigator. "The culprit is hiding in plain sight on the surface of tumour cells, so we are now developing "smart" molecules to block its function. The ultimate goal is to generate new targeted, non-toxic treatments â very different from the standard âslash and burnâ chemotherapy."

The researchers found that podocalyxin significantly expands the non-adhesive face of cells, allowing individual cells to brush aside adhesion molecules situated between tumour cells. The "freed" cells then move away from the original site to form new tumours at other sites. Also, the protein causes tumour cells to sprout microvilli, or hair-like projections, that may help propel cancer cells to other sites.

In addition, when the protein expands the non-adhesive face of cells it drags along with it a second protein called NHERF-1 â a protein shown by others to be implicated in cell growth and invasion. The researchers now believe the mechanism applies to difficult-to-treat invasive breast and ovarian cancers.

"Weâre now tapping into what causes the characteristic cell shape changes seen in cancerous tumours and possibly how these cells grow and metastasize. It gives us a whole new target for therapy," says Assoc. Prof. of Medical Genetics and stem cell expert Kelly McNagny, co-senior principal investigator. "If we can block the protein, we may be able to stop the spread of cells."

Post-doctoral Fellow Julie Nielsen, of UBCâs Biomedical Research Centre, and PhD student Marcia Graves of the Dept. of Cellular and Physical Sciences, were instrumental in designing and executing the research experiments, he adds.

Next steps involve advancing the research in animal models, designing antibodies to block the function of the protein and working with the UBC-based Centre for Drug Research and Development to identify new therapies to combat metastasizing cancer.

The researchers say information from this discovery may speed development of new therapies to within 10 years.

In 2006, more than 22,000 women were diagnosed with breast cancer and 5,300 died of it, according to estimates from the Canadian Breast Cancer Foundation. The Canadian Cancer Society estimates that approximately 2,300 new cases of ovarian cancer were diagnosed and about 1,600 women died from the disease in 2006.

Protein identified that regulates effectiveness of Taxol chemotherapy in breast cancer

Thu, 22 Feb 2007 07:58:03 PST

( from http://www.rxpgnews.com ) Cancer researchers at Georgetown University Medical Center have taken a step towards understanding how and why a widely used chemotherapy drug works in patients with breast cancer.

In laboratory studies, the researchers isolated a protein, caveolin-1, showing that in breast cancer cells this protein can enhance cell death in response to the use of Taxol, one of two taxane chemotherapy drugs used to treat advanced breast and ovarian cancer. But in order to work, they found the protein needs to be "switched on," or phosphorylated. The results were reported in the current (February 23) issue of the Journal of Biological Chemistry.

Their finding suggests it may eventually be possible to test individual breast cancer patients for the status of such molecular markers as caveolin-1 in their tumors to determine the efficacy-to-toxicity ratio for Taxol, said the studys first author, postdoctoral fellow Ayesha Shajahan, Ph.D., of Lombardi Comprehensive Cancer Center at Georgetown.

"Because breast tumors are not all the same, it is important to know the cancers molecular makeup in order to increase the efficiency, and lower the toxicity, of chemotherapy drugs, and this work takes us some steps forward in this goal," she said. "It also offers insights into why some breast cancer cells can become resistant to therapeutic drugs."

Additionally, the study identifies caveolin-1 as a new molecular target for increasing the efficacy of taxanes, according to the studys lead investigator, Robert Clarke, Ph.D., D.Sc., a Professor of Oncology and Physiology & Biophysics. "This is important because the taxanes are active drugs in breast cancer, so now that we know caveolin-1 is a new mechanism to explain how these drugs kill breast cancer cells, we can potentially take advantage of that fact to improve these agents."

The taxanes are Taxol (also known as paclitaxel) and Taxotere (docetaxel). Taxol was originally derived from the Pacific yew tree, and Taxotere is a semi-synthetic version of Taxol with slight chemical changes. These drugs stabilize a cells "microtubules," the road-like protein structures that send chemical signals to all parts of the cell, and which must be flexible if a cell is to divide. Taxanes lock these structures into place, not allowing them to change when the cell begins to divide - which is necessary for tumor growth. Research has also indicated that the drugs induce programmed cell death (apoptosis) in cancer cells by inactivating an "apoptosis stopping protein" called BCL2, thus stopping it from inhibiting cell death.

Caveolin-1 is a protein that is found in most cells under normal conditions and it is involved in an array of cellular events that ranges from vesicle trafficking to cell migration. It is, therefore, as a key regulator of multiple events within the cell.

In cancer, the expression level of caveolin-1 can vary depending on cell type. However, the precise role of caveolin-1 in cancer has been controversial: whether it acts as a suppressor or facilitator of tumor formation depends on the cell type. In human breast cancer, caveolin-1 has been known to act as a tumor suppressor since caveolin-1 expression is down-regulated during the primary stages of breast cancer. More recent studies indicate that that caveolin-1 expression is increased in more aggressive types of breast cancer.

Under the mentorship of Clarke, Shajahan sought to determine factors that regulate expression and function of caveolin-1 in the breast. In this study, the researchers show that in their breast cancer cell model that phosphorylated caveolin-1 increased cell death by activating other key regulators vital to both breast cancer progression and cell death, including BCL2, the same protein that Taxol works on; p21, which controls cell cycle progression; and the tumor suppressor p53.

If caveolin-1 isnt phosphorylated, breast cancer cells appear to be resistant to Taxol treatment, the researchers conclude. "Thus, this study opens an area of investigation in our lab that will concentrate on understanding how this multi-tasking protein can serve as a marker for chemotherapeutic drug efficacy," Shajahan said.

Gab-2 protein may spur metastasis in breast cancer

Thu, 22 Feb 2007 07:40:41 PST

( from http://www.rxpgnews.com ) A protein known for its ability to "bridge" interactions between other cellular proteins may spur metastasis in breast cancer, the diseases deadliest stage, a study from Burnham Institute for Medical Research has found.

Led by professor Gen-Sheng Feng, Ph.D., and colleagues at Burnham and Royal Victoria Hospital in Montreal, Quebec, the study ranks among the first to more precisely define the cancer role for the protein known as Gab-2. These results, to be published in the journal Oncogene, have been made available to the worldwide medical research community by priority posting online at the journals website.

The protein has been of keen research interest for its role in breast cancer, but whether it controlled metastasis or initial tumor growth was unknown. Gab-2 is one of a group of proteins known as "scaffold" or "bridge" proteins, which provide a molecular intermediary to help cell signal proteins interact.

"Although Gab-2 is highly expressed in breast cancer, it is not essential for the development of cancer," said Feng. "We found that Gab-2 is, however, essential for metastasis, or the spread of cancer. Breast cancer victims can survive before metastasis, but their chances decrease significantly when the cancer cells have spread. If we can understand precisely how Gab-2 functions in metastasis, then we might be able use this knowledge to design treatments that would block the deadly metastasis."

Feng, who studies molecular signaling in embryonic stem cells and examines signaling pathways that are involved in obesity and diabetes, has studied the roles played by Gab-2 and its chemical cousin Gab-1, in various disorders. His fundamental analyses of cell signaling for Gab-2 led him to study the protein in cancer cells.

Feng and his colleagues began by examining Gab-2s role in a pathway influenced by the cancer-causing oncogene Neu, which is implicated in nearly 30 percent of human breast cancers and associated with poor survival rates. While scientists have known that the Neu pathway drives cancer development and metastasis (and can be treated with the drug Herceptin with a certain degree of success), the molecular mechanisms that lead to breast cancer development and metastasis are not fully understood.

Feng worked with mice a special strain of mice which lacks the gene for Gab-2. The Gab-2 mutant mice were bred with two types of mice; one with an active gene that induced metastatic breast cancer tumors and another that grew breast cancer cells with low potential for metastasis.

The mutant mice showed minor effects from the initial growth of breast cancer cells, Feng and his team found, indicating that Gab-2 has little effect on inducing cancer cell growth. However, in the mice pre-disposed to metastatic breast caner, the lack of Gab-2 potently reduced metastasis rates, indicating that Gab-2 was necessary for metastasis, if not for initial tumor growth.

Since Gab-2 is a scaffold molecule and is possibly part of many signaling pathways, Fengs group wanted to determine how it influences cancer cell growth. They studied pathways known as Akt and Erk, well-known parts of the Neu oncogene pathway, in the mice lacking Gab-2 and found that while levels of Akt signals were unaffected by Gab-2s absence, Erk signals were significantly reduced.

"It appears that Akt and Erk pathways have distinctive roles in mammary tumors; initiation and growth for Akt and metastasis for Erk," said Feng. "We suspect that Gab-2 might promote mammary cell metastasis through Erk activation. This is a novel mechanism for breast cancer metastasis which makes Gab-2 a possible new target for the design of therapies for metastatic breast cancer."

Feng and his team are now looking at the other molecules that assist the scaffold protein Gab-2s effects on breast cancer metastasis.

Study shows higher mortality rates in African and African American women with breast cancer

Wed, 21 Feb 2007 07:49:07 PST

( from http://www.rxpgnews.com ) African and African American women are more likely to die of breast cancer than their white counterparts because they tend to get the disease before the menopause, suggests new research from the University of East Anglia and the Childrenï¿½s Hospital Boston in collaboration with researchers in the US and Italy.

A racial disparity in mortality rates from breast cancer in the US first appeared in the 1970s coinciding with the introduction of mammography. The new research, published in The International Journal of Surgery, posits that the reason for this is not reduced access to medical care, but because surgery in pre-menopausal women could encourage growth of the cancer.

The average age of breast cancer diagnosis in African American women is 46, compared with 57 for European Americans.

A previous study by one of the articleï¿½s authors, Dr Isaac Gukas, of the University of East Angliaï¿½s School of Medicine, Health Policy and Practice, identified a mean age of 43 for diagnosis of breast cancer in Nigerian women compared with a mean age of 64 in the United Kingdom. Over 70% of the Nigerian cases were aged below 50, compared to less than 20% of cases in the UK.

Further research published in 2005 suggested that those who underwent surgery for the disease before the menopause were more likely to relapse.

"Surgery to remove a primary tumour induces the formation of new blood vessels ï¿½known as angiogenesis. In pre-menopausal women who have high levels of oestrogen and other hormones, this may encourage the growth of the tumour," said Dr Gukas.

"Early detection, through mammography, is more effective in post-menopausal women, and more white women are diagnosed after the menopause. This could explain the disparity in mortality."

Dr Gukasï¿½s experience as a clinician treating breast cancer in Africa led him to form the hypothesis that surgery-induced angiogenesis might explain the very high early mortality and generally poor outcome of patients in that part of the world.

He also noted that African patients presented with the disease in their early 40s, although no one has yet identified why black women get the disease earlier.

"We do not intend to oversimplify this subject, but it seems clear that at least part of the phenomenon of widening mortality along racial lines could be attributed to surgery leading to accelerated tumour growth in pre-menopausal women," said Dr Gukas.

"We have the data from epidemiology. Now we need further research to confirm these observations before we explore any necessary changes in practice."

The hypothesis, if proven, has implications for all women with breast cancer, especially pre-menopausal women ?including the 20% of women in the UK who get breast cancer before the age of 50.

"We do not have enough evidence to alter treatment at present and younger women should not be deterred from having surgery. But, if further studies confirm our hypothesis, we may need to give them appropriate chemotherapy, including angiogenesis inhibitors, beforehand to ensure the best outcome," added Dr Gukas.

Breast cancers expressing IGF-1R are resistant to Herceptin

Tue, 20 Feb 2007 08:36:54 PST

( from http://www.rxpgnews.com ) Using gene chips to profile tumors before treatment, researchers at Harvard and Yale Universities found markers that identified breast cancer subtypes resistant to Herceptin, the primary treatment for HER2-positive breast cancer. They say this advance could help further refine therapy for the 25 to 30 percent of breast cancer patients with this class of tumor.

In the February 15 issue of Clinical Cancer Research, the researchers found that HER2-positive tumors that did not respond to Herceptin expressed certain basal markers, growth factors and growth factor receptors. One of these, insulin-growth factor receptor 1(IGF-1R), was associated with a Herceptin response rate that was half that of tumors that did not express IGF-1R.

They also discovered that resistant tumors continue to over-express the HER2 growth factor protein -- an important finding given that many scientists had thought that loss of HER2 was likely responsible for Herceptin resistance.

"Herceptin has revolutionized the care of HER2-positive breast cancer for many patients, but unfortunately, not for some. This work demonstrates that digging deeper into the molecular subtypes of these tumors helps us understand why some tumors are resistant and may point to ways to remedy that," said the studys lead author, Lyndsay Harris, M.D., associate professor and Director of the Breast Cancer Disease Unit at Yale University Medical Center.

If additional studies validate these findings, it may be possible to select those patients that will be resistant to Herceptin and treat them with additional drugs to restore Herceptin sensitivity, according to Harris. "Our goal is to see what the tumor tells us before any treatment starts and tailor therapy accordingly," she said.

To determine Herceptin sensitivity, investigators took a small tumor biopsy from 48 patients with newly diagnosed and operable stage II/III breast cancer. They examined the biopsy tissue using both single and multi-gene microarrays, looking for RNA that has been activated to produce proteins.

They then treated the women with a combination of Herceptin and the chemotherapy drug Navelbine weekly for 12 weeks. Although this is not the first study to test Herceptin use before surgery, it is the first to examine the use of Navelbine, a drug approved for lung cancer treatment, in combination with Herceptin to treat HER2-positive tumors. "We were motivated to use Navelbine because we found it has few side effects when used to treat metastatic breast cancer," said Harris, who conducted much of the research study at Harvard before moving to Yale.

After treatment, the tumors were surgically removed and gene chips were again used to examine RNA transcription -- making these investigators the first to use such a technique on Herceptin treated tumors. "This kind of profiling has been done to look at response to chemotherapy drugs, but not at Herceptin resistance," Harris said.

The researchers then divided tumors into groups depending on how well they responded to therapy, and examined the baseline and post-therapy RNA profiles to find genes that were more commonly expressed in Herceptin sensitive and Herceptin resistant tumors.

They first found that some single gene markers, such as HER2 and ER (estrogen receptor), did not change in the majority of tumors. "That tells us that the cancer cells are still creating HER2 surface proteins even as Herceptin is being used, and that means HER2 loss does not appear to be a mechanism of resistance in early stage breast cancer," Harris said.

Then, using multigene chips, the researchers derived a bevy of transcribed genes that likely play a role in Herceptin resistance. Some, such as IGF-1R, were suspected, because this protein is frequently over-expressed in breast tumors, Harris says, but others were not. For example, non-responding tumors were more likely to express genes associated with basal-like breast cancer, which the researchers found to be surprising. "Most basal-like tumors are HER2-negative," Harris said.

Herceptin resistant tumors were also more likely to express a variety of growth factors, suggesting that "activation of parallel pathways may release tumors from dependence on HER2 proliferation and survival," she said.

Although the study was not designed to look at outcome, the researchers determined that 42 of 48 patients had a clinical response (16 complete responses and 26 partial responses) from the neoadjuvant treatment, and five patients experienced cardiotoxicity. After a median 2.6-year-follow-up, three of 48 patients relapsed and one died of her disease.

Physical activity reduces the risk of invasive breast cancer

Thu, 15 Feb 2007 10:20:44 PST

( from http://www.rxpgnews.com )

The results provide further evidence that for most women physical activity may reduce the risk of invasive breast cancer, the researchers concluded.

Six or more hours per week of strenuous recreational activity may reduce the risks of invasive breast cancer by 23 percent, according to researchers from the University of Wisconsin Paul P. Carbone Comprehensive Cancer Center (UWCCC). Their report in the February issue of Cancer Epidemiology Biomarkers & Prevention, based on a survey of over 15,000 women, shows that exercise has a protective effect against invasive breast cancer throughout a womans lifetime.

The results provide further evidence that for most women physical activity may reduce the risk of invasive breast cancer, the researchers concluded.

To gain further insights into the mechanisms of risk reduction for breast cancer, the researchers investigated the relationship between physical activity and breast cancer risk in a population-based case control study in Massachusetts, New Hampshire, and Wisconsin.

During structured telephone interviews, the researchers questioned 7,630 women without breast cancer, 1,689 survivors of in situ, or non-invasive, breast cancer and 6,391 survivors of invasive breast cancer, all between the ages of 20 and 69. They asked detailed questions about physical activity, occupation, family history of breast cancer, menopausal status, and body mass index.

According to the researchers, women who exercised had a reduced risk of developing invasive breast cancer provided they didnt have a family history of breast cancer. This reduction in risk was apparent whether the physical activity took place early in life, in the postmenopausal years, or in the recent past.

"A woman's hormone levels naturally fluctuate throughout her life, and we have found that exercise likely offers protection against breast cancer regardless of a woman's stage in life," said Brian Sprague, a UWCCC research assistant and lead author of the study. "The take-home message for women should be that it is never too late to begin exercising."

Previous research has linked high levels of estrogen to an increased risk for developing breast cancer. Women who exercise heavily are, in general, older at the time of the first period, and tend to have irregular periods and a shortened estrogen-producing phase, which translates in a lower body exposure to estrogen, the researchers say.

Similarly, postmenopausal women who are physically active have also been shown to have lower levels of estrogen. This reduction may explain why increased physical activity reduces the risk of breast cancer, according to Amy Trentham-Dietz assistant professor at the University of Wisconsin-Madison and member of the University of Wisconsin Paul P. Carbone Comprehensive Cancer Center. Other potential mechanisms include prevention of weight gain, regulation of insulin sensitivity and alterations in immune function.

Taking all these factors into consideration, "intervention studies assessing the effect of physical activity on estrogen and other hormone exposure, and other biomarkers of risk would provide valuable insights on the mechanisms of physical activity in reducing breast cancer risk," said Trentham-Dietz.

"Further studies of population subgroups are necessary to gain a better understanding of the relation of physical activity to breast cancer risk, and to identify the groups most likely to gain benefit from it," said Trentham-Dietz. "Future research should also consider household activity in addition to recreational and occupational activities."

An integrated single genomic test would reveal ER and HER-2 status of breast cancer

Thu, 15 Feb 2007 02:38:56 PST

( from http://www.rxpgnews.com )

An integrated single genomic test could estimate the risk of cancer relapse after surgery, determine the ER and HER2 receptor status, and also gauge the sensitivity of the tumor to hormone therapy and chemotherapy.

Two critical characteristics of breast cancer that are important to treatment can be identified by measuring gene expression in the tumor, a research team led by scientists at The University of Texas M. D. Anderson Cancer Center reports in Lancet Oncology online.

Researchers developed and validated a new genomic microarray test that identifies whether a tumor's growth is fueled by the female hormone estrogen and the role of a growth factor receptor known as HER-2 that makes a tumor vulnerable to a specific drug. The status of these factors is now determined by pathology tests.

"This is one important step towards personalized diagnosis and treatment planning based on an integrated genomic test of an individual tumor," said senior author W. Fraser Symmans, M.D., associate professor in the M. D. Anderson Department of Pathology. The Lancet Oncology paper results are the latest in an effort by the research team to develop a single test to quickly and efficiently determine the characteristics and vulnerabilities of a patient's breast cancer and ultimately to guide treatment.

About 70 percent of breast cancers are estrogen-receptor positive and another 15 to 25 percent are human epidermal growth factor receptor-2 (HER-2) positive. Each receptor status requires different types of treatment.

The gene expression tests were 90 percent accurate for both receptors, which makes them comparable to, if not better than, existing pathology tests.

"This moves us closer to developing an integrated single genomic test that could estimate the risk of cancer relapse after surgery, determine the ER and HER2 receptor status, and also gauge the sensitivity of the tumor to hormone therapy and chemotherapy," says Lajos Pusztai, M.D., Ph.D., associate professor in the M. D. Anderson Department of Breast Medical Oncology, and team leader with Symmans.

ER-positive tumors are treated with estrogen-suppressing drugs such as Tamoxifen. Tumors that are HER-2 positive are sensitive to Herceptin, an antibody-based drug that binds to the HER-2 receptors, blocking them from coupling with growth factors that fuel breast cancer.

Last fall, the group published a study showing that a genomic microarray test can also predict a patient's response to chemotherapy. They also presented a paper in December showing that another genomic index predicts how an ER-positive patient will respond to hormonal therapy.

A prospective clinical trial will soon open at M. D. Anderson to use these tests to recommend treatment for patients with newly diagnosed stage I-III breast cancer.

In the Lancet Oncology paper, they employed an Affymetrix microarray to gather estrogen receptor and HER-2 receptor gene expression data from 495 breast cancer samples from seven institutions. The samples included both fine needle aspiration biopsies and traditional biopsies.

The team used 195 fine-needle biopsy samples to set gene expression thresholds that predicted ER-positive status with 90 percent accuracy and HER-2-positive status with 93 percent accuracy. They then applied those thresholds to two more validation studies involving the remaining samples, which showed that the initial results were both reliable and reproducible.

The gene expression tests disagreed with traditional immunohistochemical lab analysis of the tumors by 8 percent for ER and 11 percent for HER-2. The researchers note this degree of discrepancy is usual when different diagnostic methods are applied to the same samples.

Survey reveals that majority of breast cancer survivors do not understand the chance of recurrence

Thu, 15 Feb 2007 02:09:47 PST

( from http://www.rxpgnews.com ) A unique survey of African American breast cancer survivors at heightened risk for hereditary breast cancer has found the majority do not believe they have an increased chance of developing the cancer again.

Researchers from the University of Pennsylvania, reporting in the February issue of Cancer Epidemiology, Biomarkers & Prevention, say these findings suggest it is important to ensure that African American women understand their risk of developing cancer, and genetic counseling to address cultural beliefs and values may be one way of doing so.

"Having a personal and family history of breast cancer are known risk factors for breast cancer, and it is surprising and worrisome that most of these women with such a history don't recognize that risk," said the study's lead author, Chanita Hughes Halbert, Ph.D., assistant professor of psychiatry and Director of the Community and Minority Cancer Control Program at the University of Pennsylvania's Abramson Cancer Center.

Halbert's research focuses on understanding the socio-cultural underpinnings of cancer prevention and control behaviors among ethnically diverse populations so that interventions can be designed that reduce cancer morbidity and mortality.

One such intervention is genetic counseling that often includes testing whether a woman has a mutation in one of two genes (BRCA1/BRCA2); women with these genes are at greater risk for developing breast cancer than women without alterations in those genes.

In an earlier study, Halbert found that African American women with a family history of breast cancer had a lower risk perception than did Caucasian breast cancer survivors. In this study, she and a team of researchers at Penn attempted to tease apart the factors that might lead to this disparity, one of which, they believe, is the way survivors think about time.

"Attitudes about time are aspects of a cultural worldview," Halbert said. "We thought, based on earlier work, that African American women who were most concerned about things that might happen in the future would have a heightened perception of risk."

The researchers surveyed 95 African-American women who had a personal and family history of breast cancer that was suggestive of hereditary disease, had been treated for the disease with either lumpectomy or mastectomy, and had one intact breast. All of the women were offered the opportunity to participate in genetic counseling.

The researchers found that 53 percent of respondents felt they had the same or a lower risk of developing breast cancer again compared to other women, but that a substantial minority of the survivors (47 percent) reported that they had a higher or much higher risk.

Investigators found support for one of their hypotheses -- that women with more education were significantly more likely to perceive a higher risk of breast cancer recurrence.

But their hypothesis about time perception was wrong. Instead, perception of risk was related to how often a woman thought about the past. Women who thought more about the past were about three times more likely to report that they had a high risk of developing breast cancer again.

That finding makes sense, Halbert said, if respondents have a continued sense of vulnerability. "Because past experiences with disease may still be salient to women who think about the past a lot, these women may be likely to believe that they have a high risk of developing breast cancer again," she said.

The findings suggest that during genetic counseling, more focus should be placed on providing cancer risk information and in understanding the basis of risk perceptions, especially how they may be related to past experiences with disease, Halbert said. "We can enhance genetic counseling if we develop a better understanding of why women believe they may be at higher or lower risk," she said.

Early switch to aromatase inhibitors significantly improves survival rates in breast cancer

Mon, 12 Feb 2007 03:54:41 PST

( from http://www.rxpgnews.com )

Recent evidence shows aromatase inhibitors used alone or in follow-up after two years of tamoxifen therapy demonstrates clear and, in some cases, improved reduction of recurrence risk.

For breast cancer patients taking tamoxifen, switching to an aromatase inhibitor within three years significantly improves survival rates, according to a new study. Published in the March 15, 2007 issue of CANCER), a peer-reviewed journal of the American Cancer Society, the study reveals that the clear survival benefit was also achieved without an increased risk of death from other causes a significant risk associated with tamoxifen.

Hormone modulating therapies have made a significant impact on the survival rates of women with estrogen-sensitive breast cancer over the last two decades. The drugs are used as adjuvant to primary surgical treatment for a period of five years.

Tamoxifen was the first estrogen modulator shown to increase survival and reduce the risk of breast cancer recurrence. However, tamoxifen is associated with increased risk of death from other causes, such as strokes and endometrial cancer. Despite this risk, tamoxifen and another drug in this class, raloxifene, remain an extensively used and popular treatment.

Aromatase inhibitors, such as aminoglutethimide and anastrozole, work in a different way to lower estrogen levels. Recent evidence shows aromatase inhibitors used alone or in follow-up after two years of tamoxifen therapy demonstrates clear and, in some cases, improved reduction of recurrence risk. However, there is conflicting evidence about mortality benefits.

Led by Professor Francesco Boccardo, M.D. of the National Cancer Research Institute and the University of Genoa in Italy, researchers pooled data from two studies (828 women) comparing five year treatment with tamoxifen alone (415 women) or tamoxifen for two to three years followed by an aromatase inhibitor for the remaining treatment period (413 women).

Dr. Boccardo and his colleagues found that compared to treatment with tamoxifen alone, all cause mortality risk and breast cancer-related mortality risk both fell significantly for women switching to an aromatase inhibitor. In addition, there was no increased risk of death from other causes in women who were prescribed the aromatase inhibitor.

"This pooled analysis provides solid evidence that switching to an aromatase inhibitor following a few years of tamoxifen treatment, implies a mortality benefit over continued tamoxifen and that the benefit on breast cancer-related mortality is mainly due to the effect of switching," conclude the authors.

New approaches in breast cancer management may lead to exciting new nonsurgical tools

Mon, 12 Feb 2007 03:21:29 PST

( from http://www.rxpgnews.com )

Current research in the fields of radiology, drug therapeutics, and vaccine development has great potential to change breast cancer management.

Aggressive research currently underway brings hope of dramatic advances in breast cancer management, according to a new review. Published in the March 15, 2007 issue of CANCER a peer-reviewed journal of the American Cancer Society, the review reveals that new approaches in breast cancer imaging, investigations into the timing of chemotherapy, and research on breast cancer vaccines may lead to exciting new nonsurgical tools for the physician treating breast cancer patients. These new tools may significantly alter current screening and treatment paradigms used by surgical oncologists, as well improving the care of patients.

Our understanding of breast cancer has changed since Dr. William Halsted started performing radical mastectomies in the 1880s. Advances in genetics, immunology, and cell biology have demonstrated that breast cancer is not a single disease, but a complex family of diseases that requires fine-tuning of treatment at the level of the each individual patient. The current multidisciplinary approach to breast cancer treatmentï¿½surgery, radiotherapy, chemotherapy, hormonal therapy, targeted therapyï¿½will continue to evolve as our knowledge of the disease grows.

S. Eva Singletary, M.D., F.A.C.S, a surgeon from the University of Texas M. D. Anderson Cancer Center in Houston, discusses the latest research in breast cancer screening and management in this new review. "As we progress into the 21st century," she writes, "new treatment schema and devices outside of the surgical arena may significantly alter" current practices.

She finds that current research in the fields of radiology, drug therapeutics, and vaccine development has great potential to change breast cancer management. In radiology, 3-dimensional digital mammography, color doppler ultrasonography, and other more sophisticated technologies, such as magnetic resonance imaging (MRI), are being refined to more accurately identify the size and location of tumors, and to distinguish between benign and malignant lesions. The use of nanotechnology may provide safer imaging that capitalizes on our growing knowledge of specific genes associated with cancer.

In the area of systemic therapy, the timing of drug treatments is being altered to maximize cell death, "short-circuit" tumor growth, and minimize toxicity to the patient. Though early in development, vaccines that stimulate the patient's own immune system to attack developing tumors are being tested in animals with encouraging results. Preliminary clinical trials in breast cancer patients have also shown promising immune responses, although much remains to be done in this complex, but promising, area of research.

"During the lifetime of most surgeons practicing today," Dr. Singletary writes, "we have seen breast cancer management evolve dramatically from a paradigm centered on radical surgery to one that involves the synergistic combination of multidisciplinary approaches." She concludes, "It will be important for surgeons to stay aware of all developments that may improve the care of their patients, and to be true surgical oncologists rather than merely surgical technicians."

SPECT/CT imaging aids in better sentinel node identification in overweight women

Tue, 06 Feb 2007 11:52:21 PST

( from http://www.rxpgnews.com ) Increasing the ability to identify sentinel nodesthe very first lymph nodes that trap cancer cells draining away from a breast lesion sitehas a major impact in the treatment and outcome of breast cancer patients, possibly eliminating the need for unnecessary and painful surgery. Researchers found that using SPECT/CT imaging aids in sentinel node identificationespecially for overweight or obese women, according to a report in the February issue of the Journal of Nuclear Medicine.

Lymphoscintigraphy (a commonly performed nuclear medicine procedure that makes the lymphatic system visible to specialized cameras)used with single photon emission computed tomography (SPECT)/computed tomography (CT) imagingboosted sentinel node identification not only for the general population but also for those who were overweight. The addition of SPECT/CT with lymphoscintigraphy enhanced sentinel node identification in overweight patients with breast cancer, noted Hedva Lerman, vice chair of the nuclear medicine department at Tel-Aviv Sourasky Medical Center in Israel. Failure to identify sentinel nodes is more frequent in overweight or obese patients, and improved techniques are needed to guide surgeons to their location, said the co-author of Improved Sentinel Node Identification by SPECT/CT in Overweight Patients With Breast Cancer. She explained, While the identification of the sentinel node is an important part of surgical management approaches in breast cancer, obesity is a significant factor in why it fails and inevitably leads to occasionaland unnecessaryfull axillary lymph node dissection (a more complex surgery that removes all lymph nodes in the armpit region).

Breast cancer is the second leading cause of cancer death in this country, with women having a 1 in 8 chance of developing it during their lives. When breast cancer is suspected, women may undergo sentinel node biopsy, a minimally invasive surgical procedure used to determine whether breast cancer has spread to lymph glands under the arm, said Lerman. The biopsy requires the removal of only a few first draining lymph nodes for close review, and the lack of cancer cells in these nodes could eliminate the need for removing additional lymph nodes. Identifying the sentinel node before this surgery is key; by removing and examining it, a doctor can determine if breast cancer has spread. Accurate staging of newly diagnosed patients with breast cancer is of major importance for optimizing breast cancer patients treatment, said Lerman. Knowing whether the cancer has spread helps determine the stage and approach to treatment, she noted. Performing lymphoscintigraphy by using SPECT/CT allows detection of sentinel nodes preoperatively in more patients, thus reducing the rate of failure to identify these nodes, especially in overweight patients, said Lerman. She added, It also provides a more precise anatomical localization of the nodes prior to surgery, thus facilitating the surgical procedure.

In this study, Israeli researchers calculated their subjects body mass indexes and evaluated 220 women with invasive breast cancer by identifying sentinel nodes in three ways: using an intraoperative blue dye technique, lymphoscintigraphy (pre-operative two-dimensional imaging) and SPECT/CT lymphoscintigraphy. Researchers found that SPECT/CT lymphoscintigraphy also discovered sentinel nodes that were not identified with the intraoperative blue dye technique in a significant number of patients. As the number of integrated hybrid SPECT/CT systems evolves, our results hopefully will encourage the use of lymphoscintigraphic SPECT/CT in other centers, said Lerman. Data will continue to be collected in identifying sentinel nodes in problematic subgroups of patients with breast cancer and in those with other solid tumors where nodal staging is indicated, she said.

Epigenetic drugs, promising for breast cancer treatment

Sun, 24 Dec 2006 17:13:37 PST

( from http://www.rxpgnews.com ) Worldwide, cancer persists as one of the most important diseases that affect the human being. The knowledge on the molecular bases of cancer generated during the last decades has been successfully translated into small but significant gains in overall cancer survival rates due to better primary prevention measures, improved diagnostic methods and the development of more effective and specific therapies, collectively termed "molecular targeted therapies". In the context of these new forms of treatment, epigenetic or transcriptional cancer therapy is clearly promising.

Epigenetics refers to the function of DNA that does not depend on the coding DNA sequence itself but on the accessory molecules and mechanisms affected by DNA. It is known that epigenetic alterations are equally if not more important than classical genetic alterations to disrupt the function of tumour suppressor genes. The two most studied epigenetic aberrations common to all types of cancer are DNA hypermethylation and histone deacetylation, which cooperate to silence the expression of tumour suppressor genes, just as gene mutations and gene deletions do. The big difference between these two alternative ways that tumour cells use to inactivate tumour suppressor genes is that, while the reversal of genetic alterations is technically almost unfeasible in clinical scenarios, the function of these epigenetically inactivated suppressor genes is easily reactivated by pharmacological means. In this inaugural issue of PLoS ONE, Dr. Dueñas-Gonzalez's group from the Instituto de Investigaciones Biomédicas of the Universidad Nacional Autónoma de México and the Instituto Nacional de Cancerología, Mexico, demonstrate, for the first time, that a combination of a DNA methylation and a histone deacetylase inhibitor, can reactivate the expression of more than a thousand genes in primary tumours of breast cancer patients.

Among these reactivated genes are those implicated in the regulation of cell proliferation, cell differentiation, programmed cell death, invasion, metastasis and immune recognition of tumour cells, such as p53, p21, eighteen members of the oxidative phosphorylation pathway, interferon-regulatory factors, NM23, negative regulators of Wnt signalling and Major Histocompatibility Complex Class-I and –II genes. In addition, these drugs down-regulate genes such as ABCB5, a recently identified member of the ABC transporter family implicated in multidrug resistance, which is predominantly expressed by tumour "stem" cells. Moreover, in this proof-of-principle study, the Mexican researchers demonstrate that this combination of epigenetic drugs can be safely administered concurrently with classical cytotoxic agents such as doxorubicin and cyclophosphamide, a common drug combination employed in the primary treatment of breast cancer.

Although this study is suggestive of increased anti-tumour effects no definitive conclusions can be drawn from it regarding the clinical efficacy of this therapy, because the study is single arm and the number of patients small; however, it is clearly suggestive that the epigenetic "principle" works and calls for increased preclinical and clinical efforts toward epigenetic cancer therapy.

Researchers used "epigenetic" drugs routinely employed for non-malignant conditions One important aspect of this study, considers Dr Dueñas-Gonzalez, is that the "epigenetic" drugs used, are "very-well known" and have been routinely employed for almost 30 years to treat non-malignant conditions: the antihypertensive hydralazine and the antiepileptic valproic acid. Advocacy groups are claiming that "big pharma" companies are not interested in pursuing the preclinical and clinical development of this type of drugs –regardless of their potential antitumour efficacy– simply because they cannot be protected by patents and in consequence huge revenues cannot be expected. If the antitumour efficacy of these epigenetic drugs is eventually demonstrated, they would not only be added to the current anticancer armamentarium, but they will surely be affordable to the vast majority of cancer patients living in low and middle income countries, who find the newer anticancer agents prohibitively expensive. Dr. Dueñas-Gonzalez's group has recently completed a couple of single arm studies of this therapy with similar results and launched three placebo-controlled randomised trials in breast, ovarian and cervical cancer patients.

Breast cancer chemotherapy may deterioration in cognitive function

Sun, 29 Oct 2006 21:31:37 PST

( from http://www.rxpgnews.com ) A new study investigating the effects of chemotherapy on cognitive function in mice has confirmed what many cancer patients receiving treatment have often complained about a decline in their memory and other cognitive functions, sometimes characterized as "chemobrain".

The study, led by Dr. Gordon Winocur of the Baycrest Research Centre for Aging and the Brain, in collaboration with Drs. Ian Tannock and Janette Vardy of Princess Margaret Hospital, was conducted at Trent University. The findings are published in the September 2006 issue of Pharmacology, Biochemistry and Behavior (Vol. 85, Issue 1), which will be available online in the next week. The results were presented at a workshop held in conjunction with the 8th World Congress of Psycho-Oncology in Venice last week.

"In our study, we identified learning and memory deficits in the mild to moderate range in the drug-treated mice compared to the controls," says Dr. Winocur.

"That the deficits were relatively small is encouraging. It's important that cancer patients continue with these drugs and know that if they experience mild to moderate impairments in their cognitive functions, this level of change is potentially manageable."

While there is growing evidence from studies of cancer patients on chemotherapy that the chemobrain effect does exist, many of the studies have suffered from methodological limitations. These include small samples, less than adequate controls and failure to account for other factors, including disease-related complications and stress, which could affect performance.

This latest study, using an animal model, afforded researchers the opportunity to look at the direct effects of chemotherapy drugs on cognitive performance without interference from potentially confounding variables.

In the study, 25 healthy female mice were split into two groups: the drug treatment group received standard doses of methotrexate and 5-fluorouracil (5FU), two drugs widely used in women to prevent recurrence of breast cancer; and the control group received a saline solution. Both groups were given their treatments over three weeks.

One week after the final injection they were put through a series of spatial/non-spatial memory tests and conditional rule learning tests in a water maze. The behavioral tasks enabled investigators to assess various aspects of learning and memory associated with different brain regions. The drug treatment group scored lower on the spatial memory task (hippocampus) and the task requiring strategic and working memory components (frontal lobes), especially when there were long delay intervals, compared to the control group. The drug group was not impaired on a cued memory test or in discrimination learning, tasks that are not affected by selective damage to the frontal lobes or hippocampus.

"This indicates that the adverse effects of this treatment regimen of methotrexate and 5FU probably do not extend to all regions of the brain. It appears that the hippocampus and frontal lobes are primarily affected," says Dr. Winocur.

Because the behavioral testing was initiated two weeks after the last treatment and completed within four to five weeks, the study assessed only the short-term effects of the drugs. This is important because it raises the possibility that at longer treatment intervals there might have been some recovery of cognitive function, notes Dr. Winocur.

Elderly Breast Cancer Patients May Be Under-Diagnosed And Under-Treated

Tue, 17 Oct 2006 14:33:37 PST

( from http://www.rxpgnews.com ) Elderly patients with breast cancer who received care in a community hospital setting may have been under-diagnosed, under-staged and under-treated, according to a report in the October issue of Archives of Surgery, one of the JAMA/Archives journals.

The number of older breast cancer patients has increased along with overall elderly population, according to background information in the article. About half of breast cancer patients are older than 65 years and 35 percent are older than 70; 77 percent of breast cancer deaths occur in women older than 55. Choosing the appropriate treatment for older patients is a challenge, because many have other serious illnesses in addition to their cancer that may threaten their health and shorten their lives. Questions remain about the best screening protocols for elderly women, as well. Some current guidelines suggest that women stop having mammograms at age 70, while others provide no upper limit.

David A. Litvak, M.D., then of Michigan State University, Lansing, and now at Kaiser Permanente Medical Center, Orange County, Calif., and Rajeev Arora, M.D., used a tumor registry database to identify 354 women age 70 or older who were diagnosed with breast cancer between 1992 and 2002 at a community hospital. The researchers studied the group of women as a whole and also divided them into three age groups for analysis: ages 70 to 74 (136 patients), 75 to 79 (115 patients) and 80 or older (103 patients).

Overall, 46 percent of the patients came to their physician with breast cancer that could be felt during a physical examination. Although 72 percent of all the women and 60 percent of those age 80 and older had mammograms, they were mainly used to verify the results of the physical exammammograms uncovered previously undetected breast cancer in only 54 percent of the patients, including 38 percent of those 80 years or older. More than 70 percent of patients were in the early stages of cancer, stages I and II, at diagnosis, but evaluation of the lymph nodes to thoroughly assess the cancers progression was omitted in 36 percent of the cases (56 percent of those in women 80 or older).

About half of the women received breast-conserving surgery; however, rates of chemotherapy, radiation and hormonal therapy were lower than would be expected and were lowest among the oldest women. For example, 12 percent of all patients, 19 percent of those age 70 to 74 and 5 percent of those older than 80 underwent chemotherapy. We also noted omissions of treatment in patients with indications for adjuvant [combination] treatment, including those whose cancer had spread to the their lymph nodes or who had estrogen receptor-positive tumors, the authors write. All together, 70 patients (20 percent) had positive lymph nodes. Of these patients, 29 percent received chemotherapy. Moreover, only 17 percent of patients age 80 years or older received chemotherapy in the presence of lymph node disease, significantly less than the 70- to 74-year age group.

Although the results of this study do not confirm that these diagnosis and treatment patterns in older women lead to worse health, other evidence suggests this is the case, they continue. Contrary to many physicians beliefs, the data suggest that fit older patients derive the same benefits from treatment as do their younger counterparts, the authors conclude. The cornerstone of treatment of older breast cancer patients is an adequate geriatric assessment that helps estimate life expectancy and predict tolerance of treatment. Treatment strategies then ought to be individualized based on this assessment. Screening guidelines should also be customized to the patient; those who expect to live more than five additional years should continue having mammograms, they write.

Tissue Geometry Plays Crucial Role in Breast Cell Invasion

Fri, 13 Oct 2006 11:01:37 PST

( from http://www.rxpgnews.com ) Apropos of National Breast Cancer Awareness month, researchers with the U.S. Department of Energys Lawrence Berkeley National Laboratory (Berkeley Lab) have created a first-of-its-kind model for studying how breast tissue is shaped and structured during development. The model may shed new light on how the misbehavior of only a few cells can facilitate metastatic invasion because it shows that the development of breast tissue, normal or abnormal, is controlled not only by genetics but also by geometry. Though created specifically for the study of breast tissue, this model should also be applicable to the study of tissue development in other organs as well.

Our results reveal that tissue geometry can control the morphogenesis of breasts and other organs by defining the local cellular branching microenvironment, said Bissell, a Distinguished Scientist with Berkeley Labs Life Sciences Division, who was the principal investigator for this study. This finding is important not only for understanding how tissue and organs get their organized shapes and patterns, but may in the future reveal mechanisms to control cancer invasion and metastasis.

In a paper published in the October 13, 2006 issue of the journal Science, Bissell and her collaborators describe a study in which the branching of mouse epithelial tubules (hollow tubes made from epithelial cells that form the network of milk ducts in the mature female breast) in culture were subjected to control through a three-dimensional micropatterned assay. Using a special algorithm to quantify the extent of branching, the researchers found that the geometric shape of the tubules determines where branching takes place. This may potentially affect where and how a malignancy spreads.

These fluorescent images show how branching morphogenesis in breast tissue is determined by tubule geometry and is consistent with the idea that branching takes place where concentrations of branching inhibitors are lowest. (A) shows curved tubules, (B) bifurcated tubules and (C) fractal trees. Images (D) through (F) show corresponding branching inhibitor concentrations.

The paper is entitled: Tissue Geometry Determines Sites of Mammary Branching Morphogenesis in Organotypic Cultures. Co-authoring the paper with Bissell were Celeste Nelson and Jamie Inman, both members of Bissells research group, and Daniel Fletcher and Martijn VanDuijn, from the University of California at Berkeleys Bioengineering Department. Fletcher also holds an appointment with Berkeley Labs Physical Biosciences Division.

In mammals, breast tissue begins to morph into milk glands at the onset of puberty. In this process, called branching morphogenesis, epithelial cell tubes begin to migrate outward, invading the surrounding pad of fat cells to form a widely branched tree of milk ducts. Branching morphogenesis is known to involve a complex interplay of both intracellular and extracellular signals that within the context of the tissue determines precisely where new branches are initiated.

Said co-author Nelson, a post-doctoral bioengineer who will soon have her own research group at Princeton University, One group of cells within a tubule is instructed to form a branch or to bifurcate, whereas a neighboring group is not. While branching morphogenesis is common to many organs, including the lung, kidney and salivary gland, we still do not have a precise understanding of how spatial positioning is determined. Given that the mammary ductal network branches out from pre-existing epithelial tubules, we hypothesized that the position of cells within a tubule might provide contextual information to instruct branch site initiation.

Bissell is one of the leading proponents of the idea that a cells genetic information is supplemented by contextual information encoded within the microenvironment that surrounds the cell. To define the role of positional context, she and Nelson developed a 3-D micropatterned assay for mammary epithelial branching morphogenesis. This assay enabled them to control the initial geometry of epithelial tubules and to quantify the positions at which they branched.

In their studies, Bissell, Nelson and their colleagues engineered epithelial tubules of defined geometry by embedding functionally normal mouse mammary epithelial cells in cavities of a collagen gel. The epithelial cells formed hollow tubules, according to the size and shape of the collagen cavities. These tubules began branching out into the gel within 24 hours after being treated with epidermal growth factor. To quantify branching and to represent its magnitude and position, the researchers stained the cell nuclei with fluorescent dye and imaged them using confocal microscopy.

We confirmed that the position of branching depended on the initial geometry of the tubule, said Nelson. Increasing the length of the tubules increased the magnitude of branching, although cells still branched exclusively from the ends. Curved tubules branched preferentially from the convex side of the curve. Asymmetric branching was also observed in bifurcated tubules and trees, which preferentially branched from distal positions.

The process of normal branching morphogenesis is precise and quantitative, but invasionary; when something goes wrong the process may lend itself to metastasis. With this demonstration of how the normal function of branching morphogenesis is controlled, Bissell believes researchers can now look for ways in which faulty tubule geometry leads to malignancy.

In breast cancer, it is most often metastasis rather than the primary tumor that kills a patient, said Bissell. We have learned something really dramatic about the regulation of normal branching morphogenesis and this should help us understand how and why things go wrong. Our next step is to put pre-malignant cells cells that are already losing their way but are not yet malignant into our model and see what happens. When we do, perhaps this will provide us with new ideas for intervening and preventing pre-malignant cells from becoming fully malignant.

Ethnic variations in hormone levels may cause differences in breast cancer risk

Tue, 10 Oct 2006 12:21:37 PST

( from http://www.rxpgnews.com ) Researchers have known that a woman's natural hormone levels can affect her risk of developing breast cancer. A new study from the University of Southern California (USC) has found that the natural levels of estrogens in post-menopausal women varies by ethnicity and race, and may explain the differences in the groups' breast cancer rates. The study appears in the October issue of Cancer Epidemiology, Biomarkers & Prevention.

Using data from the Multiethnic Cohort Study, V. Wendy Setiawan, Ph.D., assistant professor of preventive medicine at the Keck School of Medicine of USC, and her colleagues determined that of the five primary ethnicities/races in the cohort, native Hawaiians have the highest risk of breast cancer--65 percent greater than whites. They also had some of the highest levels of circulating estrogens.

"We had observed that some groups, such as native Hawaiians have higher breast cancer rates compared to white women. We knew hormones are a factor, so we decided to test them," says Setiawan. "The research seems to support that idea."

The researchers also found that Japanese-American women have comparatively high estrogen levels and the second highest breast cancer risk of the five groups. "This is interesting because breast cancer rates have been increasing steadily in Japanese women who live in the United States, as well as in women who live in Japan," Setiawan says. "We think it could be caused by lifestyle changes that impact age at first menstruation or other factors."

Latinas had similar hormone profiles to whites, while women who had recently immigrated had slightly lower levels, but which were not statistically significant, the researchers found. However, Latinas' risk of breast cancer is the lowest of the groups studied.

One of the most interesting findings was that African-American women have a slightly lower post-menopausal breast cancer risk than whites, despite having comparatively higher post-menopausal hormone levels.

"It is known that before menopause, African-American women have a higher breast cancer risk than whites, as well as higher estrogen levels," Setiawan says. "It would be interesting to find out why their elevated rates do not persist after menopause, despite having comparatively higher estrogen levels."

The researchers analyzed the hormone levels in 739 postmenopausal women in the cohort who were not on hormone replacement therapy. After adjusting the hormone levels for age, body mass index, and other lifestyle factors, they then compared the levels to their ethnic/racial groups' breast cancer incidences. The study is the largest analysis of hormone levels by ethnic group, and the first large study of native Hawaiians and Latinas.

"Clearly, more work is needed to identify factors that contribute to racial and ethnic differences in hormone levels," Setiawan says.

Researchers set benchmarks for screening mammography

Tue, 26 Sep 2006 23:09:37 PST

( from http://www.rxpgnews.com ) A recent study of medical audit data funded by the National Cancer Institute (NCI) revealed that community mammography screening results surpass performance recommendations across the United States. Approximately 188 mammography facilities nationwide contributed to the study of more than 1.1 million women, who underwent at least one screening mammography exam between 1996 and 2002.

"With a cancer detection rate of 4.8 per 1,000 women, our results show that most radiologists who are reading mammograms are performing well," said Robert D. Rosenberg, M.D., lead researcher and professor of radiology at the University of New Mexico in Albuquerque. "Mammography, combined with better breast cancer treatments, appears to be helping to decrease the number of deaths from breast cancer."

Up until now, there has been no national measurement with which radiologists could compare their individual cancer detection rates.

"There have been no data available for mammographers in the United States to give context to anyone's individual performance results. All prior guidelines were best guesses from a panel of experienced radiologists," Dr. Rosenberg explained.

In the study, data were collected from six NCI-funded research sites, for a total of nearly 2.6 million screening exams assessed by 807 radiologists. Each radiologist's assessment, along with every woman's outcome within 12 months of the initial screening exam, were tallied. The radiologists included in the analysis came from urban, rural, large and small practices of different organizational structures, across broad geographic areas.

Approximately 10 percent of mammograms yielded abnormal findings, for a recall rate of 9.8 percent.

"We found that radiologists are much more likely to err on the side of caution, for a higher recall rate," said co-author Bonnie Yankaskas, Ph.D., professor of radiology at the University of North Carolina at Chapel Hill.

After additional imaging work-up, cancer was ultimately diagnosed in 4.8 of 1,000 women. When a radiologist identified significantly abnormal findings and advised that biopsy be performed immediately, 34 percent of biopsy results yielded cancer.

The majority of women examined were 40 to 70 years old. Of all reported cancers, 21.6 percent proved to be ductal carcinoma in situ, and 78.4 percent were invasive cancers. Of invasive cancers, 37.2 percent were small tumors measuring 10 millimeters or less in diameter, 41.6 percent were mid-sized tumors measuring 11 to 20 millimeters, and 21.2 percent were large invasive tumors measuring 2 centimeters and larger.

The authors hope that their findings will allow radiologists to evaluate and improve the accuracy of their individual cancer detection rates when reading mammograms.

"Recalls and additional biopsies do add to the cost and anxiety of mammography," said Dr. Rosenberg. "However, we are continually working to improve the test from both ends--finding cancers while minimizing unnecessary work-ups."

Raloxifene Reduces Breast Cancer Risk in Postmenopausal Women at All Risk Levels

Wed, 13 Sep 2006 12:02:37 PST

( from http://www.rxpgnews.com ) Raloxifene protects postmenopausal women from developing invasive breast cancer whether they are at high or low risk of developing the disease, according to a new study.

The study, published in the September 1 issue of Clinical Cancer Research, also revealed that the drug appears to reduce risk in women with a family history of breast cancer down to a similar level to women without affected relatives.

Compared with a placebo drug, the study found that use of raloxifene was associated with a 58 percent reduction in breast cancer risk in women without a family history of the disease, and an 89 percent reduction in risk for women with a family history of breast cancer.

But the researchers say they cannot explain why protection seems greatest in women who may be genetically predisposed to develop the disease.

We dont know what to make of this observation, said Marc E. Lippman, M.D., professor in the Department of Internal Medicine at the University of Michigan and the studys lead author. It could be due to chance, or there may be other factors at work that we dont know about.

But our bottom-line analysis as to why raloxifene universally reduces the risk of developing invasive cancer in women without a family history is that it interferes with the duration and concentration of estrogen, which acts as a tumor promoter in the majority of breast cancers, said Dr. Lippman.

The research team conducted a new analysis of the first large study of raloxifene, which tested the ability of the drug to prevent vertebral fractures in 7,705 postmenopausal women diagnosed with osteoporosis. The secondary endpoint of this multi-center, double-blind trial, known as MORE (Multiple Outcomes of Raloxifene Evaluation) was the drugs effect on breast cancer development; results, announced in 1999, demonstrated a 72 percent reduction in invasive breast cancer incidence after four years of raloxifene treatment, compared to use of a placebo.

The MORE trial was then extended four years to further evaluate the effect of raloxifene on breast cancer incidence in 4,011 of the original participants. Results of this trial, known as CORE (Continuing Outcomes Relevant to Evista), showed that eight years of raloxifene treatment was associated with a 66 percent decrease in invasive breast cancer incidence.

The current study was undertaken to assess the effect of raloxifene on level of breast cancer risk (higher versus lower) using data from both MORE and CORE.

Women at higher risk for breast cancer are generally older and have a greater lifetime exposure to estrogen, and the researchers found that this association held true in the reanalysis. But they also found that raloxifene reduced breast cancer risk in both women at lower and those at higher breast cancer risk, except for those women who had measurably low levels of estradiol, the major estrogen hormone in humans.

In each variable commonly associated with a higher risk for developing breast cancer − age older than 65, age at menopause, a body mass index greater than 25, higher estradiol levels, prior use of estrogen replacement and a family history of breast cancer − use of raloxifene reduced incidence of breast cancer when compared to a placebo drug, Dr. Lippman said. But it also reduced incidence in each of those variables that should have lowered risk, such as younger age, later menopause, etc., compared to use of a placebo drug.

We dont define the lowest limit of risk, the point at which toxicity associated with use of raloxifene outweighs the benefits, he said. Dr. Lippman stressed that he cannot comment on how raloxifene in this study measures up to tamoxifen use in general. He explains that although these findings come on the heels of the June publication of the 19,747-participant STAR trial, which evaluated tamoxifen against raloxifene in reducing breast cancer risk, no comparison can be made between the MORE, CORE and STAR clinical trials.

These studies looked at two different groups of women, Dr. Lippman said. Women enrolled in STAR were at high risk for developing breast cancer, so presumably, they had higher levels of estrogen in general. Women who participated in MORE and CORE were older and had osteoporoses and it is assumed that these women generally have lower levels of estrogen, because that is a risk factor for development of the disorder.

Raloxifene, also known by the trade name Evista, has not been approved by the federal Food and Drug Administration as an agent to prevent breast cancer development.

Physical activity improves survival in breast cancer patients

Mon, 11 Sep 2006 16:44:37 PST

( from http://www.rxpgnews.com ) Women who reported the highest levels of physical activity in the year before they were diagnosed with breast cancer may have higher survival, according to a new study. Published in the October 15, 2006 issue of CANCER (http://www.interscience.wiley.com/cancer-newsroom), a peer-reviewed journal of the American Cancer Society, the study found that obese and overweight women who had higher levels of moderate or vigorous recreational physical activity within one year before diagnosis tended to have better five-year survival patterns compared to other groups. Women of ideal body weight did not experience survival benefits from exercise; more remote histories of physical activity also had no impact on survival.

Identifying factors in cancer patients that predict outcome (i.e., prognosis) is important for physicians planning patient management and patients understanding their disease. In breast cancer, clinical indicators, such as tumor size, regional lymph node involvement, and estrogen-receptor status, have been shown to influence outcome. Other lifestyle factors, such as weight, may also predict disease course. While these factors are statistically associated with outcome to some degree, they may not explain all the variation which has lead researchers to search for additional prognostic factors, such as physical activity.

While exercise has been shown to be a significant factor in preventing breast cancer, its role in prognosis after diagnosis remains unclear but has also been infrequently studied. Page E. Abrahamson, Ph.D. now at the Fred Hutchinson Cancer Research Center in Seattle, led researchers while at the University of North Carolina, Chapel Hill to investigate the relationship between pre-diagnosis physical activity and survival in 1264 women with breast cancer.

The authors report that pre-diagnosis exercise did improve disease outcome. Survival modestly increased among women with body mass index (BMI) greater than 25 who reported highest levels of physical activity within one year of diagnosis. There was no benefit for women with BMI less than 25. Also, physical activity in adolescence or early adulthood had no impact on survival.

"Given that obesity is relatively well established as a poor prognostic factor in breast cancer," conclude the authors, "it is hopeful that activity may provide an opportunity to improve survival in this sub-population."

Pedigree assessment tool correctly identifies women with higher risk of breast cancer

Mon, 11 Sep 2006 16:39:37 PST

( from http://www.rxpgnews.com ) A new screening tool for the general practitioner effectively identifies patients at risk for hereditary breast cancer, according to a new study. Published in the October 15, 2006 issue of CANCER (http://www.interscience.wiley.com/cancer-newsroom), a peer-reviewed journal of the American Cancer Society, the study reveals a newly developed, simple scoring tool called the "pedigree assessment tool" (PAT) was 100 percent sensitive in identifying women at high risk for the hereditary breast cancer syndrome. The PAT outperformed another commonly used tool, the modified Gail model, in correctly assessing individual patient risk.

Only two to three percent of breast cancers are known to be the result of hereditary syndromes that is, caused by germline mutations. The most commonly recognized breast cancer genes are BRCA1 and BRCA2. While rare, inheritance of these mutated genes leads to an approximately 80 percent lifetime risk of developing breast cancer. Current management protocols offer hope to these mutation carriers that breast cancer can be either prevented or managed effectively through intensive early detection programs. Therefore, identification of the high risk patients with this hereditary cancer syndrome in the general practice is critical for early referral for genetic counseling and rigorous screening.

Several quantitative assessments are available to physicians to calculate an individual patient's risk for developing breast cancer. One example is the modified Gail model. Collecting familial and individual risk data, the tool is able to quantifiably assess both five-year and lifetime absolute risk of developing invasive breast cancer. One of its weaknesses, according to some, is that it may substantially underestimate breast cancer risk in the subgroup of women with hereditary breast cancer syndromes and is not well-suited for identifying these women.

Led by Kent F. Hoskins, M.D. of the OSF Saint Anthony Center for Cancer Care in Rockford, IL, researchers developed the PAT as a simple, scoring tool to better "identify women in a primary care setting with family cancer histories suggesting a hereditary breast cancer syndrome." In this study, they tested the PAT against the Gail model in a population of 3906 women to identify potential BRCA mutation carriers and risk-stratify them.

PAT scoring was effective at identifying the 86 high risk patients with potential BRCA hereditary syndromes. With a PAT score of 8 or greater (i.e., high BRCA probability), sensitivity and specificity were 100 percent and 93 percent, respectively. In contrast, the Gail model calculations were no better than 73 percent in regards to specificity, and that at the expense of sensitivity, which fell to 27 percent. Further comparison between the PAT and the Gail tools showed that the PAT was more effective at assigning women to the high risk BRCA group.

The authors conclude that this study "demonstrated that a simple point scoring system (PAT) performs very well in identifying women in a screening mammography population who would benefit from referral to a cancer risk clinic for genetic counseling and consideration of DNA testing of appropriate family members."

In the context of developing comprehensive breast screening tools for the general practice, the authors assert that "such a strategy could be effectively employed by combining the Gail model with a tool like the PAT."

MRI more accurately determines cancer spread into breast ducts

Mon, 04 Sep 2006 17:02:37 PST

( from http://www.rxpgnews.com ) MRI is better than MDCT for determining if and how far breast cancer has spread into the breast ducts and should be used before patients receive breast conserving therapy, a new study shows.

"Patients have a lower survival rate if their surgical margins are positive for tumor cells. A positive surgical margin is usually the result of inadequate resection of the cancer's intraductal component," said Akiko Shimauchi, MD, at Tohoku University in Sendai, Miyagi, Japan. "Accurate preoperative diagnosis of the intraductal component allows the surgeon to achieve a cancer-free surgical margin," she said.

The study included 69 patients with proven invasive cancer, 44 of which had an intraductal component, said Dr. Shimauchi. MRI correctly identified 33 of the 44 cases, while MDCT correctly identified 27. "MRI revealed the presence of the intraductal component with significantly higher sensitivity (75%) compared to MDCT (61%), Dr. Shimauchi said.

"The lesions that were missed by both examinations were the ductal extension type, i.e. the tumor included a dominant mass with an outward extension of cancer cells, with a relatively small ductal component," said Dr. Shimauchi. MRI was better able to detect the smaller ductal components than MDCT, she said.

The study also found that both MDCT and MRI "generally underestimated the length of the intraductal component," however, MRI was less likely to underestimate the length of the intraductal component than MDCT. "In our institution, surgeons err on the side of caution by using a surgical margin that is 20 mm outside the radiologically determined tumor margin," said Dr. Shimauchi. Underestimation of the length of the intraductal components by 15 mm or more was significantly less frequent with MRI (30%) compared to MDCT (55%), she said.

Core needle biopsy gives an accurate picture of gene expression

Sat, 19 Aug 2006 16:39:37 PST

( from http://www.rxpgnews.com ) The gene expression profile detected in the core needle biopsy of a breast tumour is representative of gene expression in the whole tumour. A study published today in the open access journal Breast Cancer Research confirms the reliability of core needle biopsy as a tool in breast cancer diagnosis and prognosis. The study also shows that the gene expression profile of a core needle biopsy might be more accurate than the profile of a surgical sample taken from the same tumour, after the biopsy was carried out. According to the study results, the biopsy procedure seems to trigger the expression of genes involved in wound healing as well as tumour invasion and metastasis, thus modifying the gene expression profile of subsequent surgical samples.

Rosanna Zanetti-Dällenbach from the Women's University Hospital in Basel, Switzerland and colleagues from Stiftung Tumorbank, OncoScore AG and University Hospital in Basel, analysed the gene expression profile of core needle biopsies taken from 22 women diagnosed with breast cancer. For each woman, they compared the biopsy expression profile with the expression profile of a surgical sample taken from the tumour subsequently to the core needle biopsy. Zanetti-Dällenbach et al. quantified the expression of 60 genes known to be involved in breast tumour development using a technique called reverse polymerase chain reaction (PCR). Zanetti-Dällenbach et al. also analysed the gene expression profiles of surgical samples taken from the breast tumours of 317 patients who did not undergo a core needle biopsy.

The results of Zanetti-Dällenbach et al.'s study show that the gene expression levels of the core biopsy and the surgical sample are identical for most women. But the authors find that the expression of four specific genes is significantly increased in the surgical samples compared to the core needle biopsies. In the group of women who did not get a core needle biopsy, however, the expression of these four genes is not increased. These four genes are involved in inflammation and wound repair as well as tumour invasion and metastasis. The authors conclude that their expression must therefore be modified by the core needle biopsy procedure itself. They warn that care should be taken when interpreting the gene expression profile of a surgical sample carried out following a core biopsy. Although the tumor's aggressiveness has not changed, the modified profile in surgical samples obtained after core needle biopsy might influence data interpretation with respect to prediction of risk assessment and treatment response. The core needle biopsy sample may give a cleaner, more accurate and more representative profile of the levels of gene expression in the tumour.

Ancient war paint in fight against breast cancer

Mon, 14 Aug 2006 13:19:37 PST

( from http://www.rxpgnews.com ) A plant that gave ancient Britons and Celts their blue war paint, has been found to be a rich source of the anti-cancer compound, glucobrassicin, traditionally associated with broccoli. Glucobrassicin has been found to be effective against breast cancer. The war paint, a blue dye, is obtained from Woad, a member of the Brassicaceae family.

Stefania Galletti and her team at the University of Bologna, Italy, found that the plant contains twenty times more cancer fighting chemical glucobrassicin than its relative, broccoli, which they enhanced to nearly 65 times using various treatments. This compound plays a defensive role in plants, and the researchers found that wounding the leaves can increase levels by 30%. When leaves are damaged, for example, by insects, glucobrassicin is released as a defence mechanism. Its derivatives can kill some plant pests, and also appear to have anti-tumoral properties, and are particularly effective against breast cancer.

Glucobrassicin has shown an active role in flushing out cancer-causing chemicals including derivatives of estrogen. Women with higher levels of this hormone are at an increased risk of developing breast cancer.

Woad Flowers

There have been many reports on the health benefits of broccoli and other commonly consumed vegetables from the same family. However, it has been difficult to extract enough of the broccoli compound to carry out extensive tests. Galletti's team hope that by using this cheap, rich source, in depth research can be carried out to study how this compound acts in the body.

Specimen radiography confirms success of MRI-guided breast biopsy

Mon, 14 Aug 2006 12:04:37 PST

( from http://www.rxpgnews.com ) Radiologists can help confirm that an MRI-guided breast biopsy has successfully removed the lesion by taking an x-ray of the lesion and slices of the lesion, a new study shows.

"Contrast-enhanced MRI of the breast is becoming increasingly useful in patients with lesions that cannot be detected with other techniques," said Basak Erguvan-Dogan, MD, radiologist in Breast Imaging at the University of Texas M.D. Anderson Cancer Center in Houston. "However, it is hard to confirm removal of the targeted lesion because the abnormality does not enhance after being removed from the breast," she said.

Currently, patients who have MRI-guided needle localization and excision of abnormalities may be asked to have follow-up breast MRI; if the lesion has not been successfully removed, another biopsy procedure will need to be done. "By taking x-rays of the lesion specimen, then slicing it up and taking additional x-rays, we can determine if the lesion has been removed or if additional tissue needs to be excised while the patient is still in the operating room," Dr. Erguvan-Dogan said.

Whole specimen and sliced specimen radiography was performed in 10 patients, and X-raying the lesion as a whole and in slices proved to be valuable, said Dr. Erguvan-Dogan. "In all five malignant cases, sliced specimen radiographs showed the lesion in question, helped the pathologist correctly identify the lesion while the patient was still in the operating room and helped the surgeon obtain negative surgical margins," said Dr. Erguvan-Dogan. In addition, "whole specimen radiography is able to correctly locate fractured biopsy needle localization wires, which may be removed before the patient left the operating room," she said.

Specimen radiography is routinely used in some centers after mammographically and sonographically guided needle localization and excision; however, specimen radiography following MRI-guided needle localization has not been previously reported on, Dr. Erguvan-Dogan said.

Trastuzumab effective in breast cancer cells with low HER-2 levels

Fri, 11 Aug 2006 20:14:37 PST

( from http://www.rxpgnews.com ) Northwestern University and Evanston Northwestern Healthcare researchers have discovered that the monoclonal antibody Herceptin (trastuzumab) used in combination with certain cancer chemotherapies effectively treats breast cancer tumors that produce low or undetectable amounts of the HER-2 oncogene but overexpress the growth factor heregulin (HRG), an activator of the HER-2 cancer oncoprotein. Increased levels of HER-2 are associated with poor patient prognosis, enhanced metastasis (cancer spread) and resistance to chemotherapy.

Until now it was believed that trastuzumab combined with cytotoxic drug therapy was effective only in HER-2--positive, or HER-2--overexpressing, breast cancer which represents about 25 percent of all breast cancers, said Dr. Ruth Lupu, director of translational breast cancer research at the Evanston Northwestern Healthcare Research Institute, who led the study, published in the August 10 issue of the Journal of Clinical Oncology.

Lupu is also professor of medicine at Northwestern University Feinberg School of Medicine and a researcher at The Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

The study was conducted as part of the Cancer Center's breast cancer SPORE (Specialized Program of Research Excellence) grant.

In their study Lupu and colleagues Javier A. Menendez and Inderjit Mehmi of the Evanston Northwestern Healthcare Research Institute found that HER-2 must be activated to exert its malignant effects. HER-2 is capable of being activated by either overexpression (overproduction) or transactivation -- when a protein at one location is activated by the presence of a particular protein at another location.

HRG is an activator of the HER-2 oncogene, promoting breast cancer growth and tumor formation in laboratory models. Dr. Lupu has previously shown that blocking HRG expression inhibits tumor growth and spread of breast cancer cells. HRG is expressed in a significant proportion of human breast cancer biopsies and correlates with poor prognosis.

Lupu and her laboratory group discovered that continuous production of HRG in breast cancer cells that do not overexpress HER-2 causes the receptor to be continuously activated and therefore constantly signals breast cancer cells to grow and proliferate.

Previous clinical studies have shown that trastuzumab used in combination with such cancer chemotherapy drugs as cisplatin, Taxol (paclitaxel), docetaxel, vinorelbine and cyclophosphamide in HER-2--positive breast tumors is more beneficial than the antibody used alone. This effect, termed receptor-enhanced chemosensitivity (REC), was thought to target only HER-2--overexpressing cells but seemingly had no impact on cells expressing low amounts of HER-2 protein.

In the current study, the researchers used breast cancer cells genetically engineered to produce HRG to determine if HRG-induced activation of HER-2 can cause the same biologic responses as HER-2 overexpression with regards to sensitivity to chemotherapeutic drugs, such as cisplatin and paclitaxel.

They found that overexpression of HRG promotes resistance to cisplatin-induced cell death, while co-treatment of the genetically engineered cells with trastuzumab or cisplatin produced a synergistic apoptotic (cell-killing) effect. They also found that this synergy occurred with trastuzumab and either paclitaxel or vincristine.

"Our data not only confirm that a considerable potentiation of chemotherapy efficacy occurs when combined with trastuzumab but further demonstrate that an REC effect, which has been suggested to specifically target cancer cells bearing HER-2 overexpression and has no effect on cells expressing low levels of HER-2, is equally pronounced in HRG expression and induces activation of HER-2 occurring in the absence of HER-2 overexpression," the authors said.

Results of their study also support the view that trastuzumab blocks the effect of HER-2--driven activation of anti-apoptotic and proliferative cascades in breast cancer cells exhibiting HRG-dependent--activation of HER-2. Conversely, in the absence of HRG, trastuzumab promotes this effect in cells producing low amounts of the HER-2 protein.

Further, the group's findings strongly support the idea that measuring the activity of HER-2 on the surface of breast cancer cells maybe a better and earlier marker for breast cancer progression than simply determining the level of HER-2 production in malignant tumor cells. Moreover, profiling tumors for the expression of HRG maybe of tremendous benefit for those patients whose tumors express low levels of HER-2 protein.

Breast cancer survivors change lifestyle after diagnosis

Fri, 11 Aug 2006 19:48:37 PST

( from http://www.rxpgnews.com ) Breast cancer survivors' beliefs about what may have caused their cancer are connected to whether they make healthy lifestyle changes after a cancer diagnosis. This is the finding of a research study appearing in the August 2006 issue of Psycho-Oncology by researchers at The Miriam Hospital and Brown Medical School.

"We found that breast cancer survivors who believed that an unhealthy behavior - such as consuming an unhealthy diet, contributed to their cancer - were more likely to say that they had changed that behavior since their diagnosis," says lead author Carolyn Rabin, PhD, a psychologist at The Miriam Hospital's Centers for Behavioral and Preventive Medicine. "Likewise, breast cancer survivors who believed that a healthy behavior- such as consuming a healthy diet, could ward off a cancer recurrence - were more likely to say that they had adopted that behavior since their diagnosis."

Due to advances in detection and treatment, there are now more than 10 million Americans who are cancer survivors, according to the American Cancer Society. However, researchers have not yet determined why some cancer survivors are motivated by a cancer diagnosis to make healthy lifestyle changes, while others are not. This question prompted the study by researchers at The Miriam Hospital and Brown Medical School.

The researchers cite evidence from past studies indicating that many cancer survivors are not leading healthy lifestyles { 50 percent of breast cancer survivors consume fewer than the recommended five servings of fruits and vegetables per day, 23 percent consume more than 30 percent of their calories from fat, and 28 to 43 percent lead sedentary lifestyles. In addition, more than 50 percent of cancer survivors who smoked prior to diagnosis continue to smoke.

"Adopting a healthy lifestyle is an important strategy for cancer survivors since, in addition to a cancer recurrence, they may be at increased risk for the developing other medical problems, such as cardiac or pulmonary disease, as a result of their cancer treatment. The goal of this study was to develop a better understanding of why a cancer diagnosis appears to serve as an impetus for some survivors to adopt healthy behaviors, while others do not," says Rabin.

Normal (left) versus cancerous (right) mammography image

Researchers assessed breast cancer survivors within three months of the survivor completing all surgery, chemotherapy, and/or radiation treatment for cancer and a second time three months later. Study participants completed measures assessing beliefs about the cause of their cancer; beliefs about behavioral strategies that may reduce the chance of cancer recurrence; diet, exercise, smoking, and alcohol consumption; and any changes in health practices since their cancer diagnosis.

Findings indicated that survivors who believed that unhealthy diet, insufficient exercise or alcohol consumption contributed to their cancer were more likely to modify the relevant behavior. The most robust relationship between beliefs and behavior change was found for changes in diet.

"This study suggests that cancer survivors develop their own understanding of the causes of their cancer and the behavior changes that may prevent recurrence, and then take an active problem-solving approach to help reduce risk of a future cancer," says co-author Bernardine Pinto, PhD, a psychologist at The Miriam Hospital's Centers for Behavioral and Preventive Medicine.

Given the role of health behavior changes in reducing medical risks, these findings have important implications for maintaining the health of cancer survivors. The authors note, however, that even though survivors' beliefs about what caused their cancer may prompt healthy lifestyle changes, these beliefs may not be accurate.

"This research highlights the important role that survivors' beliefs about their disease have in their life post-cancer diagnosis. Ultimately, we hope that cancer survivors will take a holistic approach to maintaining their health so that they do not dismiss an opportunity to make a healthy lifestyle change. Behavior modification may not impact their chance of a cancer recurrence, but can help reduce other serious medical risks," says Rabin.

Computer-aided detection improves early breast cancer identification

Thu, 03 Aug 2006 17:50:37 PST

( from http://www.rxpgnews.com ) Computer-aided detection improves breast cancers in both screening and diagnostic patients according to a recent study done by a private practice radiologist in Santa Barbara, CA.

The study was conducted to evaluate the impact of CAD in a non-academic setting, most notably its effect on cancer detection in both screening and diagnostic patients. The positive predictive value (PPV) of biopsy recommendations, biopsy rate, and recall rate before and after the introduction of CAD were compared. Then, size, stage, and histology of cancers detected with and without CAD findings were evaluated.

"Early detection is essential in preventing breast cancer deaths, so as a mammography specialist, I'm always looking for tools to improve cancer detection," said Judy Dean, MD, and lead author of the study. "This study began as acceptance testing for the CAD system I purchased for my mammography practice in 2002. I scanned 50 known cancer cases and 50 normal mammograms to see how the software would perform on films from my own practice and was astounded to find that it marked 90% of the cancers. I was really surprised that a computer program could achieve that level of sensitivity, so I decided to see what effect it would have when put into day-to-day use in my practice," said Dr. Dean.

"We collected data until more than a hundred cancers had been found, and then analyzed the results to compare what types of cancers were found with and without CAD assistance," said Dr. Dean. "We used the CAD system for every mammogram performed during the study, not just screening patients, and even in patients with prior surgery, breast implants, or other findings, CAD was helpful in finding more cancers."

During a 28 month period, 9,520 film-screen mammograms were interpreted. According to the study screening-detected cancers increased 13.3% with CAD assistance and 9.5% in diagnostic exams. The greatest impact was on ductal carcinoma in situ (DCIS), the most common type of non-invasive breast cancer in women, for which CAD increased cancer detection by 14.2%.

"Cancer detections were higher in both screening studies and symptomatic patients. This means that CAD should be used for all mammograms, not just routine screening examinations," said Dr. Dean. "According to the ACR, there are currently 8,881 accredited mammography facilities in the United States but only 4,000 are using CAD."

"The principal barrier with CAD is the cost, and a proposed 50% reduction in Medicare reimbursement will make the technology out of reach for most small and medium sized facilities," said Dr. Dean. "These may be the very places that need CAD the most, as prior studies have shown that CAD has the most impact for non-specialist radiologists," she said.

Do close surgical margins predict if breast cancer will return?

Wed, 02 Aug 2006 11:50:37 PST

( from http://www.rxpgnews.com ) A new study published in the August 1, 2006, issue of the International Journal of Radiation Oncology * Biology * Physics, the official journal of ASTRO, the American Society for Therapeutic Radiology and Oncology, says that cancer cells present after additional surgery for breast cancer may predict whether a woman will see her cancer return.

This year, more than 213,000 American women will learn they have breast cancer. Many women with early stage cancer prefer to have a lumpectomy, where only the cancerous lump is surgically removed, followed by radiation therapy and possibly chemotherapy. With a lumpectomy, the surgeon removes the tumor along with some healthy, non-cancerous tissue nearby. Doctors then examine it under a microscope. If the outside of the tumor, or margin, is free of cancer, it's considered to be a negative margin. If the outside of the tumor has cancer cells present, it's considered a positive margin. When it's unclear, or a very small distance, doctors call it a close margin. Women with a positive or close margin often require more surgery to make sure all the cancer is removed. This surgery is called a re-excision. Most patients with close or positive margins would be advised to undergo re-excision.

In this study conducted at Fox Chase Cancer Center in Philadelphia, doctors divided 1,044 patients with stage I-II breast cancer with close or positive margins into three groups. Group 1 included 199 patients who did not have additional surgery, group 2 had 546 patients who had additional surgery proving they were free from cancer and group 3 included 299 patients who had additional surgery and showed evidence of additional cancer. All patients received radiation therapy.

After 10 years, the number of local recurrences was the same for women who had re-excision and for women who did not have re-excision (group 1 versus groups 2 and 3 together). However, the result of the re-excision helped predict whether women would have their cancer return. Women with no residual disease at the time of re-excision (group 2) had a local control of 95 percent, while women found to have residual disease in the breast (group 3) had a local control of 91 percent.

"This study helps to clarify the role of a re-excision for a close or positive margin in women undergoing breast-conserving therapy for early-stage breast cancer," said Derek Chism, M.D., lead author of the study and a radiation oncologist now practicing at North Shore Medical Center in Peabody, Mass.

CHEK2*1100delC mutation may triple breast cancer risk

Tue, 01 Aug 2006 13:38:37 PST

( from http://www.rxpgnews.com ) A study of more than 9,000 Danish residents shows that a specific variation in the CHEK2 gene may triple a woman's risk of developing breast cancer in her lifetime. The study--the first to examine the prevalence of the CHEK2 mutation in the general population and the associated cancer risk--will be published online July 31 in the Journal of Clinical Oncology.

"Our study shows that women in the general population who carry a specific CHEK2 mutation are three times as likely as women without the mutation to develop breast cancer," said Borge G. Nordestgaard, MD, Professor and Chief Physician, Department of Clinical Biochemistry, Herlev University Hospital, Denmark, and lead author of the study. "The findings suggest that CHEK2 could serve as a useful biomarker for identifying women who would benefit from heightened, regular screening for breast cancer."

CHEK2, which belongs to a class of genes known as "tumor suppressors," is responsible for repairing DNA damage and preventing the uncontrolled division of cells, which can lead to cancer. In this study, researchers looked for a specific mutation, known as CHEK2*1100delC, which impairs the gene's ability to fix damage to DNA.

Previous case-control studies have shown an association between this specific CHEK2 mutation and breast, prostate, and colorectal cancer. Researchers designed this study to assess the prevalence of the mutation in the population at large and to examine its impact on cancer risk.

Dr. Nordestgaard and his colleagues randomly selected 9,231 Danes who had participated in the Copenhagen City Heart Study--a cohort of more than 20,000 Danish men and women that followed participants for an average of 34 years for cancer development.

The researchers found that 0.5% of all participants carried the CHEK2 mutation. Among women who carried the CHEK2 mutation, 12% developed breast cancer, compared to 5% of non-carriers. Adjusting for other factors, such as age, body mass index, and use of hormone replacement therapy, researchers found that women who carried the mutation were 3.2 times as likely as women who had normal CHEK2 genes to develop breast cancer. Those most at risk were mutation carriers on hormone replacement therapy who were more than 60 years old and overweight--who had a 24% chance of developing the disease within 10 years. The researchers found no statistically significant association between the CHEK2 mutation and prostate, colorectal, or general cancer risk.

By way of comparison, other studies have shown that BRCA 1/2 mutations occur in roughly 1% of the general U.S. population. Women with a BRCA1 or BRCA2 mutation have a dramatically heightened risk of developing breast cancer--up to an 80% chance of developing the disease during their lifetime and at a much younger age than women who do not have one of these two mutations. Life-time risk of breast cancer among women in the general population is approximately 13%.

"There are clearly a number of genetic and environmental factors in play when it comes to the development of breast cancer," said Dr. Nordestgaard. "The identification of CHEK2 as a biomarker gives us a better picture of the genetic risk factors, and may help to identify a significant subset of women who would benefit from more vigilant screening for the disease."

According to the study's authors, a key limitation of the research was that it included only white Danish women; it is not known to what extent CHEK2 mutations are found among black, Hispanic or other women, or whether the breast cancer risk associated with CHEK2 mutations among these women is of a similar magnitude to those involved in this study.

Google-like process for mammogram images speeds up interpretations

Wed, 26 Jul 2006 14:59:37 PST

( from http://www.rxpgnews.com ) To help computers provide faster "second opinions" on mammogram images showing suspicious-looking breast masses, medical physicists at Duke University are employing a Google-like approach that retrieves useful information from an existing mammogram database within three seconds. Rather than comparing the mammogram image in question to every image of breast cancer in a computer database, the new approach compares the mammogram in question to selected images that are most highly ranked for their information content.

This is analogous to how a Google search first returns a list of only those websites that it determines to have the most important and useful information on the words entered in the search.

In a pilot study that will be presented in August at the 48th Annual Meeting of the American Association of Physicists in Medicine in Orlando, the approach enabled computers to maintain their high level of accuracy while performing faster analysis. Such speed and efficiency will be important as such image databases rapidly grow larger and more complex.

Knowledge-based computer-assisted detection (CAD) systems compare mammogram images to those of known cases of breast cancer in order to aid radiologists in their diagnosis. However, as clinical image libraries grow rapidly in mammography practice, knowledge-based CAD systems get slower and less efficient.

In efforts to prevent such systems from bogging down, Duke's Georgia D. Tourassi, Ph.D. (Georgia.tourassi@duke.edu) will present a Knowledge-Based Computer Assisted Detection (KB-CAD) system that analyzes breast masses using the principles of information theory.

When a new, unknown case is presented for analysis, the KB-CAD system compares the case to mammography images in the database. It retrieves cases that are similar, those that share certain visual features and properties. If the unknown case is similar enough to a known case of breast cancer, then this would suggest the presence of cancer.

Although diagnostically accurate, this practice becomes inefficient as the image database increases in size. Therefore, the researchers incorporate an additional approach.

Instead of comparing the new unknown case with all mammography images stored in the knowledge database, the researchers restrict the analysis to the stored cases that are most informative. The selection of the most informative cases is done using an image indexing strategy based on the concept of "image entropy." Image entropy represents a measure of the disorder or complexity in the image. An image that is all black or white has zero entropy. An image of a checkerboard has low entropyit consists of an equal number of light and dark pixels. Complex images with more uniform distributions of many pixel intensity levels have higher entropy and are considered more informative in the context of the Duke system.

Normal breast tissue "can be as complex as a tumor," Tourassi says. "This is precisely the reason mammographic diagnosis is such a challenging task. Our database inlcudes normal cases as well in the decision-making process."

In the recent pilot study, the Duke researchers applied their technique to a database of 2,300 mammography images. With entropy indexing, the researchers compared a sample image to the top 600 most informative, cutting down their CAD system's processing time by one-fourth, to less than 3 seconds per query. The researchers expect to launch a larger study in a year to evaluate the clinical impact of this new approach.

Breast stem cells have features similar to 'basal' tumors

Thu, 20 Jul 2006 20:14:37 PST

( from http://www.rxpgnews.com ) The most aggressive form of breast cancer may originate from breast stem cells that have undergone genetic mishaps.

Victorian Breast Cancer Research Consortium scientists from The Walter and Eliza Hall Institute, using mouse models, have discovered that breast stem cells do not express receptors for the female hormones oestrogen or progesterone. These and other features of the stem cell resemble the aggressive 'basal' subtype of breast cancer. There is increasing evidence that breast cancer is not simply a single disease. Scientists now view breast cancer as a heterogeneous disease, made up of various subtypes. This observation has led to speculation that breast tumours are derived from different cell types that could include the breast stem cell or its descendents that have suffered genetic accidents.

This possibility has generated great interest in understanding the composition of normal breast cells including the stem cell. A question of particular interest is whether the breast stem cell expresses receptors for oestrogen and progesterone and the marker 'Her2', since these help define the subtypes of breast cancer; and also guide current approaches to therapy.

The WEHI team, together with the Eaves group in Vancouver, have found that the breast stem cell in mice is 'triple negative' for oestrogen, progesterone and Her2 receptors but does express certain 'basal cell' markers. These characteristics also define the basal subtype of breast cancer, which is more commonly seen in tumours that develop in women who are carriers of the breast cancer predisposing gene BRCA1.

These findings support previous speculation that breast stem cells, or very early descendents, are the cells from which basal tumours arise. Dr Visvader, who led the team effort with Dr Lindeman at WEHI, said, "This finding made by Marie-Liesse Asselin-Labat in our lab reinforces the need to understand the normal biology of the breast stem cell. Our hope is that this kind of research could in the long-term lead to the identification of new therapeutic targets against breast cancer, particularly the basal subtype." Currently drugs such as Tamoxifen, the aromatase inhibitors or Herceptin are ineffective against basal tumours and chemotherapy is the only option.

Dr Lindeman, who is also an oncologist at the Royal Melbourne Hospital, said that their team's findings will now be extended using excised human breast tissue and tumours. "We are fortunate that the Royal Melbourne Hospital campus is strongly committed to this type of translational research. Our hope is that this will lead to better cancer outcomes from a disease that strikes one in 11 Australian women." The team findings are published in the 19 July 2006 issue of the Journal of the National Cancer Institute.

New molecular marker of resistance to chemotherapy in breast cancer

Mon, 10 Jul 2006 20:13:37 PST

( from http://www.rxpgnews.com ) A collaborative study between the Hospital Clínic and the Hospital del Mar de Barcelona permits to establish a predictive factor in the resistance to chemotherapy in breast cancer and to establish possible therapeutic targets for the improvement of this treatment.

This study shows clinical evidence of the role played by the nuclear factor (NF)-kappaB in breast cancer and makes it a key target for new treatments, both to be aware of its existence and to predict a low chemotherapy response. If this is the case, the blocking of the factor prior to treatment is needed in order to increase the efficiency of treatment. The results of this study are the first to be published in which nuclear factor (NF)-kappaB, which promotes the survival of cells, has been specifically studied in order to observe its relevance in the prediction of response to chemotherapy.

Breast cancer is the most frequent cancer among women around the globe, with more than one million cases every year. It is the first cause of lost of potential years of life, and the second leading cause of cancer death among women. Breast cancer is one of the diseases causing more disorders to women in the developed countries because of the increase of new cases, its high mortality and the social repercussion it entails.

In Catalonia, the prevalence of breast cancer is of more than 50,000 women. Although the number of cases and incidence rate increase every year, mortality rate decreases. Survival of patients is improving, achieving a 5 year survival of almost 80%, a number higher than the European mean. The improvement of the screening programmes and the continuous improvements in treatment underlie the key of success in the decrease of mortality. Chemotherapy treatment plays an important role in recovery or increase of survival of these patients. Now, a new line to improve results consists in finding which patients are benefited from chemotherapy in order to make a personalized treatment.

This study has contributed to the understanding of one of the resistance mechanisms to chemotherapy previous to surgery in patients of locally advanced breast cancer. If the response to preoperational chemotherapy is improved, not only survival improves, but also surgeries can be less radical, preservation of the breast is possible and decrease the psychological, emotional and social impact of the treatment is achieved.

"Results show that patients with breast cancer who presented activated nuclear factor (NF)-kappaB in tumour cells prior to treatment with chemotherapy, only achieve 20% response to chemotherapy", explains Dr. Tusquets, "whereas if (NF)-ĸB is not activated, chemotherapy response increases up to 91%". Moreover, the relevance of this factor has been confirmed since the activation of (NF)-kappaB increases after chemotherapy exposure, what could explain part of the acquired chemotherapy resistance during treatment.

The repercussion of this study and the fact that it confirms clinically other cellular results permits to consider this study as a departure point for future studies regarding this factor in collaboration with other hospitals, and to be able to offer personalized treatments in the future. "Not only can we predict chemotherapy response of tumour before treatment is started, but also can we search for a mechanism to act upon the nuclear factor (NF)-kappaB, deactivate it and permit an efficient chemoterapy" concludes Dr. Montagut, the first signatory of this article.

ATM Gene Fault Doubles Breast Cancer Risk

Mon, 10 Jul 2006 19:18:37 PST

( from http://www.rxpgnews.com ) The risk of developing breast cancer is doubled in women who inherit a damaged version of a gene called ATM, according to a study published by Cancer Research UK funded scientists and collaborators in Nature Genetics today (Monday).

A team of researchers at The Institute of Cancer Research compared 433 breast cancer patients with a family history of the disease, but who dont carry faults in the breast cancer genes BRCA1 or BRCA2, with 521 healthy women. They found 12 ATM gene faults in the patient group, compared with two in the healthy group, showing that the gene is linked to breast cancer more often than would be expected by chance.

The team conducted a detailed statistical analysis of their data and estimated that carrying a faulty version of the ATM gene raises a womans risk of breast cancer by about two-fold. This takes the overall risk of breast cancer by age 70 in a carrier of the faulty gene from one in twelve to around one in six. These findings could lead to new ways of identifying women at increased risk of developing breast cancer and in treating and preventing the disease, but further research will need to be done first.

Around five to ten per cent of breast cancers are believed to be due to inherited genetic faults. Some of these are well known, such as faults in the BRCA genes, but most of the genes involved in familial breast cancer have not yet been identified. For over 20 years scientists have reported links between breast cancer and the ATM gene, but until now, there was controversy about which faults in ATM could increase the risk of breast cancer and by how much.

Study author Nazneen Rahman, professor of cancer genetics at The Institute of Cancer Research, said: Our study provides strong evidence for the first time that damaged ATM genes definitely have a moderate effect on breast cancer risk in a small number of women. Women who carry these genetic faults could benefit from targeted screening and new treatments in the future, but we need to learn much more about ATM before this information will feed into clinical practice.

Serious faults in the ATM gene are responsible for a rare, progressive, childhood disease, called ataxia-telangiectasia, which leads to severe neurological disability, as well as blood cancers and respiratory problems. People with this disorder have two faulty copies of the ATM gene, and carriers of the disease have one. It is the carriers with one faulty copy of the gene who have the higher breast cancer risk, although they are otherwise healthy.

ATM, like BRCA1 and BRCA2, is a DNA-repair gene, so women with a faulty ATM gene cannot repair damaged DNA correctly. Cells with damaged DNA can start to replicate uncontrollably and become cancer cells, which is why individuals with faulty DNA repair genes are at an increased risk of cancers, such as breast cancer.

About 150 families in the UK have members with two faulty copies of the ATM gene who are affected by ataxia-telangiectasia. Between half to one percent of the general population carry a single faulty copy of the gene. This means around 400 of the women who develop breast cancer each year in the UK are thought to carry an ATM gene fault less than one per cent of the 41,000 breast cancer cases.

Professor Michael Stratton, from The Institute of Cancer Research and The Wellcome Trust Sanger Institute, who also worked on this study and who led the team that discovered BRCA2, said: Inherited risk of breast cancer is probably caused by a combination of genes, so our work is now focused on finding out what other genetic factors are at play that cause around 15 per cent of female ATM carriers to go on to develop breast cancer.

Professor John Toy, medical director at Cancer Research UK, said: This is a significant study. Pinpointing genes that raise the risk of breast cancer will help us to gain a much clearer understanding of how the disease develops. Also by identifying individuals who could benefit from specific treatments, scientists can begin to develop drugs that could help these patients in the future. An example is a new class of anti-cancer drugs currently being developed by Cancer Research UK scientists to exploit this defect in DNA repair.

The relative risk of breast cancer associated with ATM mutations was estimated to be 2.37 (two fold). This is similar to the increase in risk seen with the CHEK2 gene, which was reported by the same group of researchers in 2002.

Some people are born with a fault in one of their genes. This does not mean that they will ever actually develop cancer, but it does mean that fewer other things need to go wrong with the rest of their DNA for disease to develop. Doctors say that these people are statistically more likely to get cancer, and that they have a genetic predisposition to the disease.

Women who have a very strong family history may have a faulty gene in their family that increases their risk of breast cancer. There are several genes faults that can increase breast cancer risk. But, so far, doctors can only test for two of them, BRCA1 and BRCA2.

Boost radiotherapy effective for ductal carcinoma in situ

Mon, 10 Jul 2006 19:07:37 PST

( from http://www.rxpgnews.com ) Radiotherapy of the whole breast followed by a boost could stop the very early stages of breast cancer from returning claim researchers from the international Rare Cancer Network in paper published online today by The Lancet Oncology. This strategy should therefore be considered in addition to surgery for patients with the breast-cancer precursor called ductal carcinoma in situ, or DCIS.

We had two main findings notes Guenther Gruber (Kantonsspital, Aarau, Switzerland), lead author of the study: "First, not using radiotherapy in young patients with DCIS resulted in an unacceptable number of women having their cancer return; and second, these patients benefit from an additional boost dose".

Boost radiotherapy, in which a "boost" of 1016 Gy of radiotherapy is given in addition to the normal radiotherapy treatment after surgery, is already known to work in invasive breast cancer, and especially so in younger women. The researchers therefore decided to try out this technique in younger women, but with DCIS, an earlier stage of breast cancer.

Dr Gruber and colleagues analysed the records of 373 women aged 45 years or younger from 18 institutions throughout the world who had DCIS and had received breast-conserving surgery. About a sixth of the patients were not given any radiotherapy after surgery; almost half received radiotherapy without a boost; and the remaining two-fifths received radiotherapy with an extra boost. The researchers found that the risk of the cancer returning decreased progressively for each of these techniques the most effective was radiotherapy with a boost.

So far, no randomised trials, the gold standard of assessment, have been done to assess the effects of boost radiotherapy in young women with DCIS. Dr Gruber therefore suggests that their results might mean that this technique will now be considered as a part of the armamentarium of breast conserving treatment, until randomised studies are done. "Of course", he adds, "radiotherapy has to be applied carefully, especially in regard to heart, lungs and the other breast".

Chest X-ray exposure increase likelihood of breast cancer among BRCA1/2 mutation carriers

Tue, 27 Jun 2006 20:29:37 PST

( from http://www.rxpgnews.com ) An analysis of 1,600 women with BRCA 1/2 mutations suggests that exposure to chest X-rays may increase the risk of breast cancer, and that exposure before the age of 20 may be linked to particularly heightened risk. The research, conducted by a consortium of European cancer centers, was the first to analyze the impact of low-level X-ray exposure among women at genetically high risk for the disease. The study will be published online June 26 in the Journal of Clinical Oncology.

"This is one of the first studies to demonstrate that women genetically predisposed to breast cancer may be more susceptible to low-dose ionizing radiation than other women," said David E. Goldgar, PhD, a lead author of the study who was the Chief of the Genetic Epidemiology Group at the International Agency for Research on Cancer in Lyon, France, at the time the research was conducted. "If confirmed in prospective studies, young women who are members of families known to have BRCA1 or BRCA2 mutations may wish to consider alternatives to X-ray, such as MRI," Dr. Goldgar added.

Researchers analyzed questionnaire data completed by more than 1,600 women who were involved in the International BRCA 1/2 Carrier Cohort Study (IBCCS) a collaborative European study of women who carry BRCA 1/2 mutations. While all women were carriers, not all had developed breast cancer. The questionnaire asked whether a woman had ever received a chest X-ray, whether she had received chest X-ray before age 20, after age 20, or during both periods, and how many X-rays she had been exposed to during each timeframe.

The study found that women with BRCA 1/2 mutations who reported ever having a chest X-ray were 54% more likely to develop breast cancer than women who had never undergone the procedure. In addition, women who were exposed to X-rays before age 20 had a 2.5-fold increased risk of developing the disease before age 40, compared with women who had never been exposed.

"Since BRCA proteins are integral in repairing damage to breast cells, we hypothesized that women with BRCA 1/2 mutations would be less able to repair damage caused to DNA by ionizing radiation," said Dr. Goldgar. "Our findings support this hypothesis and stress the need for prospective studies."

Investigators noted two primary limitations of the study. The first was the potential for "recall bias," meaning that women who had developed breast cancer might be more likely to remember receiving an X-ray than women who had not been diagnosed with the disease. The second was the lack of data on the specific dose and timing of radiation that was received.

"Effect of chest X-rays on the risk of breast cancer among BRCA1/2 mutation carriers in the IBCCS Study," Nadine Andrieu et al, INSERM Emi00-06 et Service de Biostatistique de l'Institut Curie, France.

Raloxifene Effectively Reduce Breast Cancer Risk

Wed, 21 Jun 2006 03:50:37 PST

( from http://www.rxpgnews.com ) Raloxifene and tamoxifen are both effective in reducing the risk of invasive breast cancer, but each has potential disease and quality of life side effects that women and their physicians will need to consider, according to two reports and an editorial published in the June 21 issue of JAMA.

Tamoxifen is a selective estrogen receptor modulator (SERM) that has been used to treat both early and advanced breast cancer for more than three decades, according to background information in the article. Raloxifene is a second-generation SERM currently used as a medication for the prevention and treatment of osteoporosis. But clinical trials have shown it may have a role in reducing the risk of invasive breast cancer in postmenopausal women.

Victor G. Vogel, M.D., M.H.S., from Magee-Womens Hospital, University of Pittsburgh School of Medicine, and colleagues from The National Surgical Adjuvant Breast and Bowel Project (NSABP), conducted a randomized clinical trial (Study of Tamoxifen and Raloxifene or STAR trial) at nearly 200 clinical centers throughout North America. Patients were 19,747 postmenopausal women with an average age of 58.5 years with an increased five-year breast cancer risk. The study patients were randomized to receive oral tamoxifen (20 mg/day) or raloxifene (60 mg/day) over five years.

There were 163 cases of invasive breast cancer in women assigned to tamoxifen and 168 in those assigned to raloxifene (incidence, 4.30 per 1,000 vs. 4.41 per 1,000), according to the study authors. There were fewer cases of noninvasive breast cancer in the tamoxifen group (57 cases) than in the raloxifene group (80 cases), while there were 36 cases of uterine cancer with tamoxifen and 23 with raloxifene; however, neither of these differences were statistically significant. No differences were found for other invasive cancer sites, for ischemic heart disease events, or for stroke. Thromboembolic events (such as blood clots in the lung or deep veins) occurred less often in the raloxifene group and there were fewer cataracts and cataracts surgeries in that group. The number of osteoporotic fractures in the two groups was similar. There were no differences in the total number of deaths or in causes of death.

The authors suggest that primary care physicians, who are the most involved in preventive care, have not prescribed tamoxifen because it is viewed as a toxic cancer drug. In contrast, raloxifene is well known to the primary care community and is widely prescribed for the prevention and treatment of osteoporosis in postmenopausal women. More than 500,000 women in the United States are currently taking raloxifene, the majority of whom are older and at lower risk of breast cancer than are the women in the STAR trial.

In conclusion, the researchers write: This trial confirms the previously reported benefit of raloxifene in reducing the risk of invasive breast cancer and indicates that raloxifene is as active as tamoxifen in this regard. If raloxifene is approved by the Food and Drug Administration for the prevention of breast cancer, primary care physicians may be more willing, given their experience with raloxifene, to prescribe it for breast cancer chemoprevention than they have been to prescribe tamoxifen.

In a related paper, Stephanie R. Land, Ph.D., from the University of Pittsburgh and colleagues from the NSABP STAR trial compared differences in patient-reported outcomes focused on quality of life, and symptoms in the STAR participants. The patient-reported outcomes were evaluated with standardized surveys.

No significant differences existed between the tamoxifen and raloxifene groups in patient-reported outcomes for physical health, mental health, and depression, although the tamoxifen group reported better sexual function, the authors found. Although mean (average) symptom severity was low among these postmenopausal women, those in the tamoxifen group reported more gynecological problems, vasomotor symptoms, leg cramps, and bladder control problems, whereas women in the raloxifene group reported more musculoskeletal problems, dyspareunia (pain during sexual intercourse), and weight gain.

The NSABPs STAR trial, with its large-scale symptom evaluation and well-powered quality of life substudy, provides a comprehensive, detailed view of the patient experience using raloxifene and tamoxifen. Both of these agents are indicated for prevention in large populations, so these results can be widely used as tools in decision making or in helping a woman anticipate and cope with the sequelae of her chosen agent, the authors conclude.

This year, more than 200,000 women in the United States will be diagnosed as having invasive breast cancer, William J. Gradishar, M.D., from the Northwestern University Feinberg School of Medicine, and David Cella, Ph.D., from the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, write in an accompanying editorial. The past 20 years of research translating an understanding of basic biology into therapeutics has led to major improvements in the survival and quality of life of patients who carry a diagnosis of breast cancer.

The results of the STAR trial offer a pragmatic stepping stone to the next prevention trial in breast cancer. Raloxifene, if not superior to tamoxifen, may be more acceptable to clinicians presenting the option of a preventive drug.

The breast cancer chemoprevention sky now includes 2 shining STARs tamoxifen and raloxifene. Although neither is a supernova, their benefits include prevention of breast cancer in postmenopausal women at increased risk and, in the case of raloxifene, reduction of fractures related to osteoporosis. Perhaps because the clear benefits are limited to these end points, the relatively modest adverse event profiles and minimally impaired quality of life experienced by these women still may not be enough to convince primary care physicians to be more aggressive than they have been to date in breast cancer chemoprevention.

Safe side effect profile for HER-2 positive breast cancer patients using trastuzumab

Tue, 06 Jun 2006 01:28:37 PST

( from http://www.rxpgnews.com ) Researchers in the North Central Cancer Treatment Group (NCCTG) have shown that patients who receive trastuzumab at the same time as post-chemotherapy radiation treatments for HER-2 positive breast cancer have no more risk for major side effects or complications than those who do not receive the drug.

This study resulted from NCCTG clinical trial N9831, from which breakthrough treatment findings were presented at ASCO 2005. "The original N9831 study showed that trastuzumab reduced the recurrence of HER-2 positive breast cancer about 50 percent," says Dr. Halyard, a radiation oncologist at Mayo Clinic Arizona and lead author of today's study. "We hoped also to show that trastuzumab did not add complications to radiation treatment, and the current study has certainly proven that, providing good news for many women."

About 25 percent to 30 percent of breast cancers produce an overabundance of a growth-promoting protein called human epidermal growth factor receptor (HER-2). These tumors tend to grow faster and are generally more likely to recur than tumors that do not overproduce HER-2. Trastuzumab is the first identified monoclonal antibody designed specifically to attack this overexpressed protein, and is used as a follow-on treatment to chemotherapy. A monoclonal antibody is a laboratory-engineered protein that helps the body's immune system fight foreign invaders such as cancer.

Dr. Halyard's study looked at the side effects related to adding trastuzumab to radiation therapy. In the 1,460 patients who received radiation in the original N9831 group, there was no significant difference in the incidence of skin reactions, pneumonitis, dyspnea, cough, esophageal dysphagia or neutropenia between those who received trastuzumab (908), and those who did not (552). Additionally, the researchers report that within the group of 1,286 patients who received trastuzumab, those who had radiation (908) were no more likely to have cardiac complications than those who did not (378).

MR spectroscopy significantly reduces need for breast biopsy

Wed, 31 May 2006 17:05:37 PST

( from http://www.rxpgnews.com ) In a study featured in the June issue of Radiology, researchers found that imaging suspicious breast lesions with magnetic resonance (MR) spectroscopy reduced the need for biopsy by 58 percent. The investigators, from Memorial Sloan-Kettering Cancer Center in New York, discovered that with the addition of MR spectroscopy to their breast MR imaging (MRI) protocol, 23 of 40 suspicious lesions could have been spared biopsy, and none of the resultant cancers would have been missed.

"All cancers in this study were identified with MR spectroscopy. There were no false-negative results," said Lia Bartella, M.D., lead investigator and assistant professor in the Department of Breast Imaging at Memorial Sloan-Kettering. "With the addition of MR spectroscopy to our breast MRI exam, we found that the number of biopsies recommended on the basis of MRI findings decreased significantly. These results should encourage more women to take this potentially life-saving test."

MRI is playing an increasingly important role in the screening of women at high risk for breast cancer. One drawback of the technology, however, has been a considerable number of breast biopsy procedures recommended on the basis of imaging findings, which turn out to be benign. With MR spectroscopy, the radiologist is able to see the chemical make-up of a tumor, so in most cases, he or she can tell without biopsy whether or not the lesion is cancerous.

"Breast tumors have elevated levels of choline compounds, which are a marker of an active tumor," Dr. Bartella said. "By performing a brief MR spectroscopy procedure after an MRI scan, which takes only 10 additional minutes, we can noninvasively see which tumors show elevated choline levels, and therefore which lesions are likely malignant. This eliminates the need for biopsy to find out what the tumor is made of."

In Dr. Bartella's study, 56 patients with 57 breast lesions underwent MRI first, followed by MR spectroscopy. Biopsy was performed after imaging, and results were compared.

At biopsy, there were 31 malignant lesions (54 percent) and 26 benign lesions (46 percent). All 31 malignant lesions were diagnosed correctly with MR spectroscopy (100 percent sensitivity), and 23 of 26 benign lesions were diagnosed correctly (88 percent specificity). The remaining three benign lesions showed elevated choline levels, even though they turned out to be benign at biopsy. Researchers are still exploring why certain types of benign lesions would have elevated choline levels, despite their non-malignant status.

Overall, in 23 of 40 lesions of unknown histologic type (58 percent), biopsy could have been prevented if patients had undergone MR spectroscopy during their MRI exam, and all cancers would have been detected.

"MR spectroscopy is fast and well tolerated, and could be readily incorporated into a breast MRI examination," said Dr. Bartella. "By reducing the number of benign biopsies recommended at MRI, the use of MR spectroscopy will not only reduce patient morbidity, but will save unnecessary anxiety, cost and time for both the patient and the medical staff."

Dr. Bartella hopes that in the future, MR spectroscopy will be incorporated into routine diagnostic breast MRI exams, which will prevent most patients from having to return to the imaging center for a second examination.

"By working to improve this technology, we hope to improve the acceptability and cost-effectiveness of this imaging technique," Dr. Bartella concluded. "The door to breast MR spectroscopy in the clinical setting is now beginning to open."

Secret herb in tests to stop breast cancer patients' hot flushes and night sweats

Sun, 30 Apr 2006 19:10:37 PST

( from http://www.rxpgnews.com ) Researchers at the University of Manchester are testing a secret herb in a bid to stop the severe hot flushes that besiege breast cancer patients on hormone treatment.

Professor Alex Molassiotis, of the School of Nursing, Midwifery and Social Work, says the herb - one of the mint family, found in any kitchen - is thought to stop the hot flushes and night sweats which can be so bad that some women have to change their clothes three or four times a night.

It is traditionally used by Mediterranean women undergoing the menopause, but Professor Molassiotis cannot name it as he and his team are carrying out a double blind trial (neither the patient nor the doctor is allowed to know whether they are in the group taking the herb or a placebo).

The women are taking hormone treatment to lower oestrogen and progesterone levels as these affect the growth of some breast cancer cells. This can lead to early or revisiting menopause with symptoms such as anxiety, dry skin, bone thinning and hot flushes, with some women having up to 30 flushes a day. It is too risky for them to take Hormone Replacement Therapy (HRT) as this will increase the hormone levels again. Instead they are advised to cut out tea, coffee and nicotine, try alternative remedies or a certain type of anti-depressant.

Professor Molassiotis said: "It is hoped that the herbal remedy will be simpler and cheaper to take, as well as more effective, thus improving the lives of women who need all their energy to fight the disease."

He and his team are now recruiting 170 volunteers for the randomized trial, half of whom will take the phytooestrogen herb in the form of a pill and half of whom will take a placebo, from Greater Manchester and Cheshire. Only breast cancer patients who have or are receiving hormone treatments for their cancer are allowed to take part, and only if they experience at least one hot flush a day of moderate and above severity for at least a month. The treatment will be for a total of three months, taking one pill a day. The team will assess the volunteers' hot flushes four times over six months from starting the trial with questionnaires and a blood sample.

Terahertz imaging may reduce breast cancer surgeries

Tue, 25 Apr 2006 19:36:37 PST

( from http://www.rxpgnews.com ) A promising new technique to ensure complete tumor removal at breast cancer excision is introduced in the May issue of Radiology.

Researchers used light waves in a newly explored region of the electromagnetic spectrum--the terahertz region--to examine excised breast tissue and determine if the removed tissue margins were clear of cancer, with good results. This technology has the potential to eliminate the need for multiple surgeries and tissue samples to get clear surgical margins.

"We found that terahertz light could reliably distinguish between normal breast tissue, tumor and even early-stage 'in situ' cancers in excised tissue samples," said Vincent P. Wallace, Ph.D., lead investigator at TeraView, who worked with Addenbrooke's Hospital in Cambridge, England, in conducting the study. "This technology could aid the surgeon in immediately identifying residual cancer after the main tumor has been removed, thus minimizing the need for additional surgical procedures."

Currently, excised tissue samples must be sent for histopathologic examination, which typically takes several days. Thus, surgeons don't know if all the tumor has been removed until well after the surgical procedure has been completed, and often, repeat surgeries have to be scheduled. For the first time, however, terahertz imaging has the potential to eliminate the need for subsequent procedures by allowing the surgeon to analyze tissue samples during the initial excision procedure.

Terahertz light is located between the infrared and microwave portions of the electromagnetic spectrum. The researchers found that by placing a slice of excised breast tissue on a special quartz plate and exposing it to terahertz light, the light waves reflected from the tissue contained unique information about its state. The researchers were able to distinguish both invasive and noninvasive breast carcinomas from healthy tissue.

Twenty-two excised breast tissue samples were obtained from 22 women who underwent either wide local excision or mastectomy to remove breast cancer. All samples were first sliced and imaged with terahertz light, and then submitted for histopathologic analysis. Imaging took less than five minutes.

"There were substantial differences in the optical properties of normal and diseased tissue," Dr. Wallace said. The size and shape of the diseased regions at terahertz imaging were compared with those at histopathologic examination, with good results. All but three samples yielded invasive cancers. In total, there were two invasive lobular carcinomas, 14 invasive ductal carcinomas, three mixed invasive ductal and lobular carcinomas, two cases of pure ductal carcinoma in situ and one dense radial scar.

In breast cancer excision surgery, the aim is to remove the entire tumor with an adequate margin of normal tissue, while minimizing the amount of healthy tissue being removed. If a histopathologist analyzes the tissue and finds tumor at or near the edges, this indicates that there is a higher chance of cancer recurrence. A second operation is required to remove more tissue, involving additional hospital resources and increased risk of patient morbidity. Thus, there is a clinical need to accurately define the margins of the tumor during surgery.

Three-dimensional breast stem cell cultures reveal unexpected subtleties in malignancies

Tue, 25 Apr 2006 17:27:37 PST

( from http://www.rxpgnews.com ) Stem cells and how to boost them is hot on the research agenda. But stopping them could be critical too, as evidence implicating stem cells in cancer is mounting.

In the human breast, up to 20 per cent of all tumours are now suspected to originate in stem cells. Now scientists from the Icelandic Cancer Society and the Faculty of Medicine, University of Iceland have grown three-dimensional breast cell cultures to reveal unexpected subtleties about these stem cells that could explain why they spawn malignancies.

These stem cells, Valgardur Sigurdsson remarked during the EuroSTELLS Conference in Venice, Italy (19-21 March), could become targets for cancer treatment, leading to new therapies that wipe out cancer at its source. The hope is that they might also become useful tools to test new drugs.

"People have long suspected there should be a stem cell population in the human breast gland," said Sigurdsson who is part of the ESF-funded team led by Thorarinn Gudjonsson. A 'virgin' breast, before pregnancy, is very different to a fully functioning, milk-producing breast. With lactation, the breast becomes fully differentiated, and once this stage is over, it involutes. This cycle of proliferation, differentiation and apoptosis also happens in every menstrual cycle and in a more dramatic form during pregnancy. "This caught our attention, and has driven our research," Sigurdsson pointed out.

Breast cancer almost always occurs in the luminal epithelial compartment, which is also where milk is produced. Perhaps it is not surprising then, that stem cells reside in this compartment. In 2002, Thorarinn Gudjonsson, successfully isolated cells from the human breast with stem cell properties.

Gudjonsson immortalised these cells and grew them in three dimensional matrix that mimics the real, living tissue. Biologists have long relied on 2-dimensional cell cultures as the basic tool of their trade. But there is a big difference between a flat layer of cells and culturing cells in three-dimensions. The Icelandic researchers, realizing just how much a cells context matters, used the 3-D cell culture pioneered by Mina Bissell, at the Lawrence Berkeley National Laboratory in California. "We can build up a 3-D breast structure similar to what you have in vivo," says Gudjonsson.

"You can analyse cell-cell interactions and signaling pathways in these cells during morphogenesis and in cancer progression." The Icelandic researchers are now focusing their efforts on how endothelial cells convey signals to stem cells in normal breast formation and in cancer. In collaboration with another Icelandic research team, the Gudjonsson lab is now unraveling the role of tyrosine kinase receptors and their downstream signaling events.

The benefits of these 3-D assays are manifold. "This is a useful system for drug screening and testing new drugs as well as for understanding cancer progression," says Gudjonsson.

Chemotherapy gel - Polymer based therapy for breast cancer

Tue, 25 Apr 2006 17:22:37 PST

( from http://www.rxpgnews.com ) Women who undergo surgery for breast cancer followed by radiation therapy often experience breast deformities that can only be corrected through reconstructive surgery. Researchers at the McGowan Institute for Regenerative Medicine, in collaboration with bioengineers at Carnegie Mellon University, have developed a polymer-based therapy for breast cancer that could serve as an artificial tissue filler after surgery and a clinically effective therapy. Their findings, based on studies with mice, will be presented at 10:15 a.m., Tuesday, April 25 at the World Congress on Tissue Engineering and Regenerative Medicine, April 24 to 27, at the Westin Convention Center in Pittsburgh.

"Although radiation therapy is the standard treatment for breast cancer following surgery, it is expensive, time consuming and increases the cosmetic deformity caused by surgery," said Howard D. Edington, M.D., associate professor of surgery and surgical oncology at the University of Pittsburgh and faculty member at McGowan. "We sought to develop a possible alternative to radiation therapy that would not only release chemotherapy slowly to kill the cancerous cells left behind after surgery but that also would fill in the dimples and sometimes quite significant indentations that are common after breast surgery and radiation."

To test their idea, the researchers encapsulated a common breast cancer chemotherapy drug, doxorubicin, in microspheres, or beads, and then mixed them with a gelatin made of a polymer substance. Mice with breast cancer tumors were treated by inserting the gel under the skin next to the mammary gland. The researchers found that they could successfully control the delivery of chemotherapy over a period of 30 days and that the tumors were completely eradicated compared to a control group of mice that were implanted with the gel insert without chemotherapy.

"Through further research and testing, our goal is to develop this into a clinical treatment for women undergoing breast cancer surgery," said Dr. Edington who also is chief of surgery at Magee-Womens Hospital. "This treatment may help decrease the occurrences of breast deformity. With more studies under our belt, we believe this approach could eventually represent an alternative to breast radiation after surgery."

According to Dr. Edington, clinical trials on women with breast cancer will follow additional laboratory studies. A paper detailing these results will be published in the Journal of Biomedical Materials Research.

STAR Study: Raloxifene is as effective as Tamoxifen in reducing Breast Cancer Risk

Thu, 20 Apr 2006 17:12:37 PST

( from http://www.rxpgnews.com ) The Study of Tamoxifen and Raloxifene, or STAR, is a clinical trial designed see how the drug raloxifene compares with the drug tamoxifen in reducing the incidence of breast cancer in postmenopausal women what are at increased risk of the disease. One of the largest breast cancer prevention studies ever, STAR took place at more than 500 centers across the United States, Canada, and Puerto Rico.

Initial results of STAR show that the drug raloxifene is as effective as tamoxifen in reducing the breast cancer risk of the women on the trial. In STAR, both drugs reduced the risk of developing invasive breast cancer by about 50 percent. In addition, within the study, women who were assigned to take raloxifene daily and who were followed for an average of about four years, had 36 percent fewer uterine cancers and 29 percent fewer blood clots than the women who were assigned to take tamoxifen. Uterine cancers, especially endometrial cancers, are a rare but serious side effect of tamoxifen. Both tamoxifen and raloxifene are known to increase a womans risk of blood clots.

Osteoporosis Drug Raloxifene Shown to be as Effective as Tamoxifen in Preventing Invasive Breast Cancer Initial results of the Study of Tamoxifen and Raloxifene, or STAR, show that the drug raloxifene, currently used to prevent and treat osteoporosis in postmenopausal women, works as well as tamoxifen in reducing breast cancer risk for postmenopausal women at increased risk of the disease. In STAR, both drugs reduced the risk of developing invasive breast cancer by about 50 percent. In addition, within the study, women who were prospectively and randomly assigned to take raloxifene daily, and who were followed for an average of about four years, had 36 percent fewer uterine cancers and 29 percent fewer blood clots than the women who were assigned to take tamoxifen. Uterine cancers, especially endometrial cancers, are a rare but serious side effect of tamoxifen. Both tamoxifen and raloxifene are known to increase a womans risk of blood clots. STAR, one of the largest breast cancer prevention clinical trials ever conducted, enrolled 19,747 postmenopausal women who were at increased risk of the disease. Participants were randomly assigned to receive either 60 mg of raloxifene (Evista®) or 20 mg of tamoxifen (Nolvadex®) daily for five years. The trial is coordinated by the National Surgical Adjuvant Breast and Bowel Project (NSABP), a network of cancer research professionals, and is sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health. This optimistic news from STAR is a significant step in breast cancer prevention, said John E. Niederhuber, M.D., currently providing leadership at NCI. These results, once again, demonstrate the critical importance of clinical trials in our efforts to establish evidence-based practices.

"In 1998, the landmark Breast Cancer Prevention Trial showed that tamoxifen could reduce the risk of invasive breast cancer in premenopausal and postmenopausal women by nearly 50 percent," said Norman Wolmark, M.D., NSABP chairman. "Today, we can tell you that for postmenopausal women at increased risk of breast cancer, raloxifene is just as effective, without some of the serious side effects known to occur with tamoxifen."

Women taking either drug had equivalent numbers of strokes, heart attacks, and bone fractures. Both raloxifene and tamoxifen are known to protect bone health; it is estimated that half a million postmenopausal women are currently taking raloxifene by prescription to prevent or treat osteoporosis. Additionally, the initial results from STAR suggest that raloxifene does not increase the risk of developing a cataract, as tamoxifen does. Although no drugs are without side effects, tamoxifen and raloxifene are vital options for women who are at increased risk of breast cancer and want to take action, said Leslie Ford, M.D., associate director for clinical research in NCIs Division of Cancer Prevention. For many women, raloxifenes benefits will outweigh its risks in a way that tamoxifens benefits do not.

The STAR researchers also tracked known menopausal side effects that occur with both drugs and monitored the participants quality of life. The data show that side effects of both drugs were mild to moderate in severity, and quality of life was the same for both drugs.

Participants in STAR are now receiving information about which drug they were taking. Women assigned to raloxifene will continue to be provided with the drug until they have completed five years of treatment. Those women assigned to tamoxifen can choose to continue taking tamoxifen or to receive raloxifene to complete their five years of treatment.

Study details include:

STAR enrolled 19,747 women. This data analysis is based on the 19,471 women for whom complete study information was available.

The numbers of invasive breast cancers in both groups of women were statistically equivalent. Among the 9,745 women in the raloxifene group, 167 developed invasive breast cancer, compared to 163 of 9,726 women in the tamoxifen group.

More than half of the women who joined STAR had had a hysterectomy and, therefore, were not at risk of uterine cancer. For those women with a uterus, 36 of 4,732 who were assigned to take tamoxifen developed uterine cancers (mainly endometrial cancer) compared to 23 of 4,712 women who were assigned to take raloxifene.

In STAR, women in the raloxifene group had 29 percent fewer deep vein thromboses (blood clots in a major vein) and pulmonary embolisms (blood clots in the lung) than women in the tamoxifen group. Specifically, 87 of 9,726 women in the tamoxifen group had a deep vein thrombosis compared to 65 of 9,745 women taking raloxifene. In addition, 54 of 9,726 women taking tamoxifen developed pulmonary embolisms compared to 35 of 9,745 women taking raloxifene.

The number of strokes occurring in both groups of women was statistically equivalent: 53 of 9,726 women in the tamoxifen group and 51 of 9,745 women in the raloxifene group had a stroke during the trial. There was no difference in deaths from strokes: 6 of 9,726 women in the tamoxifen group and 4 of 9,745 women in the raloxifene group died from this event. Women at increased risk of stroke (those with uncontrolled hypertension or uncontrolled diabetes, or a history of stroke, transient ischemic attack, or atrial fibrillation) were not eligible to participate in STAR.

While tamoxifen has been shown to reduce, by half, the incidence of lobular carcinoma in situ (LCIS) and ductal carcinoma in situ (DCIS), raloxifene did not have an effect on these diagnoses. (LCIS and DCIS are sometimes called noninvasive breast cancers.) Of the 9,726 women taking tamoxifen, 57 developed LCIS or DCIS, compared to 81 of 9,745 taking raloxifene. This result confirms data reported in 2004 in a large study of raloxifene, the Continued Outcomes Relevant to Evista (or CORE Trial).

Breast implants don't cause cancer - Study

Thu, 20 Apr 2006 15:49:37 PST

( from http://www.rxpgnews.com ) The longest follow-up study to date of cancer incidence among women with silicone breast implants shows having implants does not put women at an increased risk for cancer, in fact, breast implants were actually shown to be associated with a decreased breast cancer risk.

That's according to research led by Joseph McLaughlin, Ph.D., cancer epidemiologist with the Vanderbilt-Ingram Cancer Center and the International Epidemiology Institute, and colleagues at the Karolinska Institute in Stockholm, Sweden. Their research will appear in the April 19, 2006 issue of the Journal of the National Cancer Institute.

McLaughlin and colleagues studied 3,486 Swedish women who had cosmetic breast implantation for the first time from 1965 to 1993 using data collected from the Swedish Inpatient Register and Cancer Register, among other extensive records collected in Sweden. "They have the best cancer registries in the world, going back almost 50 years," said McLaughlin.

He followed women over an average of more than 18 years, but some were tracked for up to 40 years. "It is the longest follow-up of women with breast implants for cancer incidence seen in the literature. It includes more than 2,200 women who were followed for 15 years or more after breast implantation and over 700 women who were followed for at least 25 years."

McLaughlin said he was not surprised to find that the women with implants had a decreased risk of breast cancer. "They tend to be thin, have smaller breasts, have children at a younger age, and all of these things are associated with a decreased risk of breast cancer," he said.

Women in the study did show an increased risk for lung cancer, but McLaughlin attributes the outcome to the number of women with implants who are smokers, rather than any effects from the implants. "Women in Sweden who have breast implants smoke much more than the general population."

McLaughlin said the take home message is women with breast implants should not be concerned about an increased risk for cancer. "This is one in a series of reassuring study results that shows there is no credible evidence to indicate an excess risk of any form of cancer due to breast implantation."

Breast Cancer Prognosis May Improve With Newer Chemotherapy

Sun, 16 Apr 2006 22:33:37 PST

( from http://www.rxpgnews.com ) An updated analysis of findings from three major consecutive clinical trials of breast cancer treatment conducted over the past twenty years indicates that women who have breast cancer with lymph node involvement and estrogen-receptor negative tumors have a lower rate of recurrence and risk of death with treatment with newer chemotherapies, according to a study in the April 12 issue of JAMA.

Breast cancer estrogen-receptor status (ER - how cells respond to specific hormonal therapies) helps identify patients who benefit from endocrine therapy. With appropriate endocrine therapy, patients with ER-positive disease have substantially better prognoses as a group than do those with ER-negative disease. Evidence is accumulating that improvements in chemotherapy disproportionately benefit patients with ER-negative tumors.

Donald A. Berry, Ph.D., of the University of Texas M. D. Anderson Cancer Center, Houston, and colleagues examined whether breast cancer patients who have lymph node involvement and ER-negative tumors benefit more from recent improvements in supplemental chemotherapy than do women with ER-positive tumors treated with tamoxifen. The researchers compared disease-free and overall survival according to ER status among 6,644 patients enrolled in 3 consecutive randomized trials of chemotherapy conducted by the Cancer and Leukemia Group B and the U.S. Breast Cancer Intergroup. The trials compared (1): 3 regimens of cyclophosphamide, doxorubicin, and fluorouracil (January 1985 to April 1991); (2) 3 doses of doxorubicin concurrent with cyclophosphamide, with or without subsequent paclitaxel (May 1994 to April 1997); (3) sequential doxorubicin, paclitaxel, and cyclophosphamide with concurrent doxorubicin and cyclophosphamide followed by paclitaxel, and also 3-week vs. 2-week cycles (September 1997 to March 1999).

The researchers found that for ER-negative tumors, chemotherapy improvements reduced the relative risk of recurrence by 21 percent, 25 percent, and 23 percent in the 3 studies, respectively, and 55 percent comparing the lowest dose in the first study with biweekly cycles in the third study. Corresponding relative risk reductions for ER-positive tumors treated with tamoxifen were 9 percent, 12 percent, and 8 percent in the 3 studies, and 26 percent overall. The overall death rate reductions associated with chemotherapy improvements were 55 percent and 23 percent among ER-negative and ER-positive patients, respectively. All individual ER-negative comparisons and no ER-positive comparisons were statistically significant.

The absolute improvement in 5-year disease-free survival was 22.8 percent for ER-negative patients, as compared with 7.0 percent for ER-positive patients, and the difference for overall survival was an improvement of 16.7 percent for ER-negative patients vs. 4.0 percent for ER-positive patients.

"Our study has 2 substantive clinical implications. First, although patients with ER-positive breast tumors may reasonably opt for chemotherapy, they should recognize that the benefits are not great as compared with those for patients with ER-negative disease. The benefits of intensive and extensive chemotherapy for unselected patients who have ER-positive disease treated with tamoxifen are modest at best. Whether such patients should opt for chemotherapy will depend on their attitudes toward the associated negative sequelae. In the years ahead, it is likely that we will have better predictors that will allow clinicians to determine which patients with ER-positive disease truly benefit from the addition of chemotherapy."

"Second, with advances in chemotherapy, patients with ER-negative tumors have had sequentially improved outcomes and their prognoses now approach those of optimally treated patients with ER-positive disease. For patients with ER-negative disease, the overall disease-free survival and overall survival benefits of modern intensive and extensive chemotherapy considered in our study are substantial," the author conclude.
(JAMA. 2006;295:1658-1667. Available pre-embargo to the media at www.jamamedia.org)

Estrogen May Not Be a Risk Factor for Carcinoma Breast

Thu, 13 Apr 2006 22:45:37 PST

( from http://www.rxpgnews.com ) Postmenopausal women treated with estrogen therapy for seven years did not experience an increased risk of breast cancer, according to a study in the April 12 issue of JAMA.

The Women's Health Initiative (WHI) Estrogen-Alone trial, which randomized women with prior hysterectomy to conjugated equine estrogens (CEE) or placebo, was stopped earlier than planned because of increased stroke incidence and no reduction in risk of coronary heart disease. In contrast to substantial epidemiological evidence associating exogenous (originating externally) estrogens with increased breast cancer incidence, preliminary analyses found fewer breast cancers in women in the CEE group, prompting a detailed updated analysis of breast cancer incidence and mammographic reports.

Marcia L. Stefanick, Ph.D., of Stanford University, Stanford, Calif., and colleagues with the WHI study, analyzed the data from the CEE-alone group of the WHI study to determine the effects of CEE on breast cancers and mammographic findings. The study included 10,739 postmenopausal women aged 50 to 79 years with prior hysterectomy who were randomized to CEE or placebo at 40 U.S. clinical centers from 1993 through 1998. Mammography screenings and clinical breast examinations were performed at baseline and annually. All breast cancers diagnosed through February 29, 2004, are included. Participants received a dose of 0.625 mg/d of CEE or an identical-appearing placebo.

In an analyses of all events (n = 237 cases) occurring prior to intervention termination, after an average follow-up of 7.1 years, nonsignificant reductions were observed for invasive breast cancer (20 percent lower rate) and for total breast cancer (18 percent lower rate) in women randomized to CEE, when compared to the placebo group. The annualized rates were 0.28 (104 cases in the CEE group) and 0.34 (133 cases in the placebo group). In further analyses, fewer breast cancers with localized disease were diagnosed in the CEE group than in the placebo group (31 percent lower rate), while the incidence of cancers of more advanced stage was comparable in the 2 groups. A similar reduction was found for ductal carcinomas, but not for lobular disease.

After the first year, the percentage of mammograms with abnormalities requiring follow-up was substantially higher in the CEE group compared with the placebo group (9.2 percent vs. 5.5 percent). Each year thereafter, the percentage of mammograms requiring follow-up was significantly higher in the CEE group resulting in a cumulative percentage of 36.2 percent in the CEE group and 28.1 percent in the placebo group over the course of the trial. However, this difference was primarily in assessments requiring short interval follow-up.

"In conclusion, CEE alone for 7 years does not increase breast cancer incidence in postmenopausal women with hysterectomy, and may decrease the risk of early stage disease and ductal carcinomas. This result is in clear contrast to the WHI trial of CEE combined with medroxyprogesterone acetate in women with a uterus, which showed a significant increase in breast cancer incidence over a mean of 5.6 years of follow-up. Both trials showed a substantial increase in the frequency of mammograms requiring follow-up from the first year onward. However, this increase was seen only for recommended short-interval follow-up mammograms in the Estrogen-Alone trial, whereas it applied also to those with suspicious abnormality or highly suggestive of malignancy in the estrogen plus progestin (E + P) trial. Initiation of CEE alone in women after hysterectomy should continue to be based on careful consideration of potential risks and benefits for a given individual," the authors write.

Appetite-Inducing Hormone Receptor Y1 Found Active in Breast Cancer

Tue, 11 Apr 2006 21:34:37 PST

( from http://www.rxpgnews.com ) A hormone receptor with regulatory roles as diverse as food intake, fear response, and cardiovascular function may also be involved in breast cancer, according to UC researchers.

The UC research team, led by Hassane Amlal, PhD, and Sulaiman Sheriff, PhD, report their laboratory findings on the hormone, neuropeptide Y, and its receptor in the April edition of the journal Cancer Research.

Earlier studies have shown that neuropeptide Ys receptor, known as Y1, is overproduced in human ovarian, prostate and breast cancers. This study, however, is the first to demonstrate that the Y1 receptor is actually working in breast cancer cells and can be turned on by excessive estrogena known cause of about 60 to 70 percent of breast cancers, they say.

The high incidence and activity of the Y1 receptor in human breast tumor cells suggests that it may play an important role in breast cancer, explains Dr. Sheriff, a UC research assistant professor in the department of surgery.

Pilot data suggests that about 40 percent of all breast cancer patients have increased levels of the Y1 receptor, he says.

We knew this receptor was overproduced in breast cancer tissue, adds Dr. Amlal, a research assistant professor in the department of internal medicine, but now the real question is what does it do in breast cancer cells, and how can we use it as a target to fight cancer.

The UC researchers were able to slow the growth of breast cancer cells with abnormally high levels of the Y1 receptor by treating them with neuropeptide Y hormone produced by chemical synthesis.

This finding gives us a promising new investigational target in the fight against breast cancer, the authors report. If we can find a way to selectively activate the Y1 receptor, we can limit breast cancer growth in the body.

Further studies of the Y1 receptors role, they explain, may ultimately lead to more targeted drug therapy for many breast cancer patients.

According to the American Cancer Society, more than 214,000 women and men will be diagnosed with breast cancer in 2006. About 19 percent will die from the disease.

Social isolation increases breast cancer death risk

Tue, 11 Apr 2006 14:15:37 PST

( from http://www.rxpgnews.com ) Breast cancer patients who have no close relatives or friends are more likely to die of the disease than those socially integrated, says a study.

According to the study by scientist Candyce H. Kroenke, women diagnosed with breast cancer should know that people around them can make a difference in whether they survive the disease, reported news portal All Headline News.

The study appearing in the Journal of Clinical Oncology found that socially isolated women, including those with few relatives or friends, were 66 percent more likely to die from all causes and twice as likely to die from breast cancer.

Women who had no close relatives or friends were three and four times more likely to die from breast cancer, respectively, than those with 10 or more close relatives or friends.

The study finds those who had no living children had a nearly six-fold increased risk of death from breast cancer in comparison to those with six or more living children.

New risks identified after early breast cancer

Mon, 10 Apr 2006 13:57:37 PST

( from http://www.rxpgnews.com ) A new study of women with early stage, localized breast cancer identifies new patterns and risk factors for invasive disease that may influence how patients are treated. Published in the May 15, 2006 issue of CANCER (http://www.interscience.wiley.com/cancer-newsroom), a peer-reviewed journal of the American Cancer Society, the study reveals that patients with lobular carcinoma in situ (LCIS) are actually at higher risk of developing advanced stage tumors than previously thought. In addition, women with ductal carcinoma in situ (DCIS) who are under 50 years old, African-American or Hispanic are at increased risk of developing advanced stage invasive tumors.

In situ lesions, such as DCIS and LCIS, are early generation cancer cells that have not yet invaded adjacent tissue. The diagnosis of DCIS and LCIS has been increasing up to 7-fold since 1980, according to U.S. statistics. The increase is hypothesized to be due primarily to more screening mammograms and breast biopsies.

The significance of these confined lesions in the course of breast cancer continues to be explored. Current research indicates that DCIS and LCIS clinically have different courses and prognoses, and consequently, should have different treatments. Oncologists recommend surgery for DCIS, considered a precursor to same breast invasive cancer. In contrast, observation after biopsy is recommended for uncomplicated LCIS, which is thought to have little invasive risk but may be a risk factor for later breast cancer. A few small studies have suggested that LCIS has a risk for same and contralateral invasive tumors, prompting some to recommend bilateral mastectomy in high risk patients.

Researchers led by Christopher I. Li, M.D., Ph.D. of the Fred Hutchinson Cancer Research Center in Seattle reviewed data from 37,692 DCIS and 4,490 LCIS patients from 1988 to 2002 to identify demographic and tumor characteristics that are risk factors for invasive disease and the pattern of invasive disease that DCIS and LCIS develop.

One notable finding is that LCIS patients were at greater risk than DCIS patients for invasive lobular carcinoma (ILC), suggesting LCIS to be a precursor lesion to ILC, rather than simply a risk factor. Specifically, LCIS patients were five times more likely to develop ILC and slightly less likely to develop invasive ductal carcinoma (IDC) compared to DCIS patients. The authors also found that LCIS patients had higher rates of ipsilateral invasive breast cancer, but similar rates of contralateral invasive breast cancer, compared to DCIS patients suggesting that "localized treatment for LCIS may be warranted."

Among DCIS patients, women under 50 years old as well as Hispanic and African-American women were at greater risk for advanced stage invasive breast cancer, which is a more lethal form of the disease, than older and Caucasian women. Possible risk reduction strategies, conclude the authors, include increasing the recommended frequency of "screening women diagnosed with DCIS at a young age" and "improving the follow-up and screening of black women and Hispanic white women with DCIS."

This study has potential impact not only on in situ treatments but also risk stratification and follow-up recommendations for women with early stage breast cancer.

COX-2 Inhibitors Significantly Reduce Risk of Cancer

Mon, 03 Apr 2006 23:39:37 PST

( from http://www.rxpgnews.com ) Results from a new, five-year study show that regular use of popular prescription pain relievers may reduce the risk of breast cancer by up to 71 percent and may offer similar benefit in the prevention of prostate, colon and lung cancers.

We believe this is the first study to show that selective COX-2 inhibitors have significant chemopreventive effects against breast cancer, says Dr. Randall Harris, professor and director of the Center for Molecular Epidemiology and Environmental Health in The Ohio State University College of Medicine and lead author of the study.

The results come from a larger, case-control study of NSAID use and its impact upon the four leading types of cancer in the United States: breast, lung, prostate and colon cancer. NSAIDs are non-steroidal, anti-inflammatory drugs that block the COX-2 enzyme pathway that is often activated in inflammation, cancer, heart disease and other disorders.

Harris and his colleagues studied the use of celecoxib (Celebrex), rofecoxib (Vioxx), regular aspirin, low-dose aspirin, ibuprofen and acetaminophen among 323 women with breast cancer from 1999-2004.

They compared the results with those from a control group of 649 cancer-free women matched for age, race and county of residence.

They discovered that women who used NSAIDs on a regular basis had less breast cancer. Specifically, they found that those who used celecoxib or rofecoxib for at least two years appeared to benefit the most, experiencing a 71 percent reduction in risk of breast cancer. Ibuprofen use over the same period was associated with a 64 percent reduction, while regular aspirin offered a 51 percent reduction in risk of the disease.

On the other hand, acetaminophen, which has a negligible effect upon COX-2 activity, and low-dose aspirin provided no significant change in the risk of breast cancer.

The COX-2 signaling pathway is important in cancer because when its activated, it can stimulate many key steps in cancer development, including cell division, inhibition of cell death, angiogenesis (the creation of new blood vessels to nourish growing tumors) and metastasis, says Harris, who is also a member of the OSU Comprehensive Cancer Center.

Harris says his research group is only midway through analyzing data from the other parts of the study, but adds that early results suggest that regular use of selective COX-2 inhibitors appears to provide about the same magnitude of protection from prostate, lung and colon cancer.

These results suggest strong potential for regular use of these drugs in cancer prevention. Still, we know these drugs may have side effects, so we are not advising people to go out and start taking them until more studies confirm that they are safe and effective, says Harris.

Celebrex is still widely used for pain relief, but Vioxx was pulled off the market in 2004 following reports of heightened risk of heart attacks.

Its clear that we need to have multiple retrospective and prospective studies to validate these findings, says Harris, who has been studying the impact of COX-2 inhibitors for many years. Eventually, we may find that regular intake of a low dose of a COX-2 inhibitor may be enough to reset the COX-2 cascade and safely protect people against cancer.

Prediction model to Determine Recurrence in Breast Cancer

Mon, 03 Apr 2006 14:43:37 PST

( from http://www.rxpgnews.com ) International researchers have developed a prediction model to assist doctors in determining the chance of recurrence of cancer in high-risk breast cancer patients who have undergone a mastectomy followed by radiation therapy. The study was published in the April 2006 issue of the International Journal of Radiation Oncology*Biology*Physics, the official journal of ASTRO, the American Society for Therapeutic Radiology and Oncology.

The study, a joint effort bringing together doctors from Taiwan and the United States, set out to develop a clinical prediction model superior to the current benchmark (tumor size and the effect on lymph nodes) for the recurrence of breast cancer in patients who have had their breast removed and undergone radiation therapy. Their prediction model takes into account five different risk factors when assessing a patient's chances of having their cancer return. They include, status of the lymph nodes near the armpit, how well the patient is accepting estrogen boosts, how many lymph nodes were affected, age at diagnosis and primary tumor size.

The doctors found that the prognostic score and predictive index are useful in estimating recurrence in breast cancer patients after mastectomy and for approximating the benefits of radiation therapy. Doctors would then evaluate these factors to determine whether the patients had a low, intermediate or high risk of the cancer returning. Patients with a high risk of the cancer returning would need to undergo a course of radiation therapy to keep the cancer at bay, while those in the lower risk group were able to safely forgo the additional treatment.

"This prediction model is important because identifying the higher risk patients sooner will allow doctors to more aggressively treat those cancers, in the hopes of giving patients a higher chance for a cure," said Skye Hongiun Cheng, M.D., lead author of the study and a radiation oncologist at Koo Foundation Sun Yat-Sen Cancer Center in Taipei, Taiwan.

HOXB13 and IL17BR in breast cancer predicts risk of recurrence

Mon, 03 Apr 2006 07:12:37 PST

( from http://www.rxpgnews.com ) Mayo Clinic researchers report that the expression of two novel genes within the tumors of women with early stage breast cancer may allow identification of women who are and are not at risk for early relapse or cancer-related death. Results of the study are published in the April 1 issue of Clinical Cancer Research.

"The HOXB13 and IL17BR gene profile was previously discovered as a potential marker of relapse in hormone-receptor positive breast cancer treated with tamoxifen," says Matthew Goetz, M.D., who co-led the project with James Ingle, M.D. and Fergus Couch, Ph.D. "Our new study shows that the marker is only useful for identifying women with a higher risk in the setting of lymph node-negative breast cancer."

The study, which was conducted by researchers at Mayo Clinic, Harvard Medical School and Arcturus Bioscience, tested whether the expression levels of two genes within women with early stage breast cancer affected the outcomes of women with estrogen receptor-positive breast cancer. The research team examined tissue from 206 postmenopausal women enrolled in a prospective study conducted by the North Central Cancer Treatment Group (NCCTG). They tested the level of gene expression of HOXB13 and IL17BR from paraffin-embedded tumors and found that the 2-gene expression ratio was an independent marker of early breast cancer relapse or death in lymph node-negative breast cancer.

"We believe that these findings are clinically important and corroborate the accumulating laboratory data which suggests that the HOXB13 gene is critically involved in breast cancer metastases," says Dr. Goetz. "Further research is needed to determine whether more aggressive or additional treatments will improve the outcomes of women identified to be at high risk by means of this marker."

Breast cancer is diagnosed in approximately one million women each year, and claims the lives of over 40,000 in the United States. More than two-thirds of all breast cancers are hormone positive, and most of these are early stage (lymph node-negative).

Failures in the Management of Elderly Women with Breast Cancer

Wed, 29 Mar 2006 12:57:37 PST

( from http://www.rxpgnews.com ) Breast cancer is one of the highest-profile diseases in women in developed countries. Although the risk for women younger than 30 years is minimal, this risk increases with age. One-third of all breast cancer patients in Sweden, for example, are 70 years or older at diagnosis. Despite these statistics, few breast cancer trials take these older women into account. Considering that nowadays a 70-year-old woman can expect to live for at least another 1216 years, this is a serious gap in clinical knowledge, not least because in older women breast cancer is more likely to be present with other diseases, and doctors need to know whether cancer treatment will affect or increase the risk for these diseases.

In 1992, guidelines were issued to the Uppsala/Örebro region in Sweden (with a population of 1.9 million) that all women with breast cancer should be able to receive equal treatment. At the same time, a breast cancer register was set up to record details about patients in the region, to ensure that the guidelines were being followed. Sonja Eaker and colleagues set out to assess data from the register to see whether women of all ages were receiving equal cancer treatment.

They compared the 5-year relative survival for 9,059 women with breast cancer aged 5084 years. They divided them into two age groups: 5069 years, and 7084 years. They also categorized the women according to the stage of breast cancer. They looked at differences between the proliferative ability of breast cancer cells, estrogen receptor status, the number of lymph nodes examined, and lymph node involvement. The researchers also compared types of treatmenti.e., surgical, oncological (radiotherapy, chemotherapy, or hormonal)and the type of clinic the patients were treated in.

They found that women aged 7084 years had up to a 13% lower chance of surviving breast cancer than those aged 5069 years. Records for older women tended to have less information on their disease, and these women were more likely to have unknown proliferation and estrogen receptor status.

Older women were less likely to have their cancer detected by mammography screening and to have the stage of disease identified, and they had larger tumors. They also had fewer lymph nodes examined, and had radiotherapy and chemotherapy less often than younger patients. Current guidelines are vague about the use of chemotherapy in older women, since studies have included only a few older women so far, but this did not explain why these women received radiotherapy less often. Older women were also less likely to be offered breast-conserving surgery, but they were more likely to be given hormone treatment such as tamoxifen even if the tumors did not show sign of hormone sensitivity. The researchers suggest that this could be because since chemotherapy tends to be not recommended for older women, perhaps clinicians believed that tamoxifen could be an alternative.

The researchers admit that one drawback of their study is that there was little information on the other diseases that older women had, which might explain why they were offered treatment less often than younger patients.

However, the fact remains that in Sweden, women older than 70 years are offered mammography screening much less often than younger womendespite accounting for one-third of all breast cancer cases in the countryand those older than 74 years are not screened at all.

Eaker and coworkers' findings indicate that older women are urgently in need of better treatment for breast cancer and guidelines that are more appropriate to their age group. Developed countries, faced with an increasingly aging population, cannot afford to neglect the elderly.

Pregnant women should not ignore breast cancer symptoms

Tue, 28 Mar 2006 21:08:37 PST

( from http://www.rxpgnews.com ) Ultrasound provides a safe and accurate method of detecting breast cancers in pregnant women, as well as assessing response to chemotherapy, according to a study appearing in the April issue of Radiology. Investigators at the M. D. Anderson Cancer Center in Houston recently studied the largest group of women to date who were both diagnosed and treated for breast cancer during pregnancy.

"Ultrasound identified 100 percent of cancers in our study, and mammography demonstrated 90 percent," said Wei T. Yang, M.D., chief investigator of the study and associate professor of diagnostic radiology at the M. D. Anderson Cancer Center, Breast Imaging Section. "We want young women to know that symptomatic breast cancer that occurs during pregnancy can be imaged, diagnosed and treated while pregnant, so they should not wait to seek medical attention if they start to have suspicious symptoms."

Hormonal changes during pregnancy and lactation create an increase in breast volume and firmness, making detection of breast masses difficult. Additionally, the need for immediate investigation and treatment in these cases is complicated by safety concerns for a developing fetus.

In the study, 23 women were diagnosed with 24 breast cancers. Seventeen tumors were diagnosed with a combination of ultrasound and mammography, four were diagnosed with ultrasound alone, and three were diagnosed with mammography alone. Mammography revealed 18 tumors in the 20 women who had mammograms (90 percent).

Ultrasound demonstrated all 21 tumors in all 20 women who had ultrasound exams (100 percent). Additionally, ultrasound depicted the spread of cancer to the lymph nodes in 15 of 18 women (83 percent) who had this area evaluated.

Invasive ductal carcinoma comprised the majority of cancers (18 patients). Sixty percent of women had stage III cancer, and 30 percent had stage II. Only one woman had stage I breast cancer, and the remaining woman had stage IV cancer with metastases to the liver.

Young women of child-bearing age do not typically have routine mammograms, so a growing cancer may not be found by the patient or her physician until it has progressed to a more serious stage.

Because of the advanced stage of cancers in this study, 16 patients (70 percent) underwent anthracycline-based chemotherapy in the second and third trimesters in an attempt to shrink the tumors. This type of chemotherapy poses minimal risk to the developing fetus and is the preferable method of treatment for pregnant women, in whom radiation treatments and surgery are usually avoided. Twelve of these 16 women underwent ultrasound to assess tumor response to chemotherapy.

Dr. Yang found that ultrasound provided an accurate depiction of treatment response in all 12 patients. "Not only can imaging help stage these cancers by assessing the lymph nodes in women who are candidates for chemotherapy, but it can also be used as a tool to assess response to chemotherapy, to determine if the treatment is effective or if a different treatment approach is necessary," said Dr. Yang.

Dr. Yang recommends that ultrasound be used as the initial imaging modality in symptomatic pregnant women. She adds that mammography should be used in women diagnosed with invasive or in situ cancers, as it may demonstrate cancerous microcalcifications not visible with ultrasound.

Breast cancer is estimated to complicate one in 3,000 to one in 10,000 pregnancies. Cancers in young women of child-bearing age usually appear as painless palpable masses. However, symptoms can include nipple discharge, skin changes and persistent or progressive unilateral breast swelling or engorgement.

Weight training benefits mind and body of breast cancer survivors

Mon, 27 Mar 2006 16:34:37 PST

( from http://www.rxpgnews.com ) Weight training significantly improves the quality of life of women recently treated for breast cancer, according to a new study. Published in the May 1, 2006 issue of CANCER, a peer-reviewed journal of the American Cancer Society, the study indicates six months of twice weekly exercise that improved strength and body composition was enough to result in improvements in the overall physical and emotional condition of the patients. This is the first randomized trial to study the effects of weight training on quality of life in breast cancer patients.

Newly diagnosed and treated breast cancer patients often suffer from a multitude of quality of life limiting complaints, including insomnia, weight gain, chronic fatigue, depression, and anxiety. While efficacious treatments for breast cancer have progressed rapidly in recent years, developing new management strategies for these secondary complaints, often related to the treatment itself, is only a recent area of study.

Exercise has been identified as a possible treatment for quality of life-limiting symptoms. A recent review of the effect of aerobic exercise on quality of life among recently treated breast cancer survivors indicated an effect only half as large as the effect noted from six months of strength training. This study represents the first exploration of the effect of strength training on quality of life among breast cancer survivors.

Tetsuya Ohira, M.D. of the Division of Epidemiology and Community Health at the University of Minnesota and colleagues evaluated the efficacy of weight training to improve depressive symptoms and quality of life in breast cancer survivors. Eighty-six women within 36 months of treatment were treated with either a weight training exercise program or no treatment.

Compared to no exercise regimen, weight training improved the women's overall physical and psychosocial quality of life. Significant improvements in lean body mass and upper body strength had the greatest impact on symptoms. "Changes in body composition and strength," conclude the authors, may empower these women with "a sense of return to feeling in control of their bodies that may translate into feeling greater efficacy in other areas of life."

Million Women Study: Not all breast cancers' risk are increased by HRT

Fri, 24 Mar 2006 13:29:37 PST

( from http://www.rxpgnews.com ) Recent research presented today at EBCC-5 from the million women study found that taking Hormone Replacement Therapy (HRT) increased the risk of some types of breast cancer, but not others.

Scientists analysed the data from the UK study to try and find a link between HRT and the type of breast cancer that developed. The research found that women who took HRT had an increased risk of developing lobular cancer (affecting the cells in the ducts of the milk-producing glands) and tubular cancer. There was not such an increased risk of developing ductal breast cancer, the most common type of breast cancer that affects the cells lining the milk duct. There was no increase in the risk of medullary breast cancer, a kind of cancer that is common in women with a genetic predisposition to breast cancer.

The study demonstrated that women who had taken combined HRT (oestrogen and progesterone) had an even greater risk of developing lobular and tubular breast cancer than women on oestrogen only HRT. The researchers also discovered similar findings for women with breast cancer in situ - when the cancer has not spread to the surrounding tissues in the breast or other parts of the body. Women that took HRT had a significantly greater risk of developing lobular cancer in situ than ductal carcinoma in situ.

G. Reeves who presented the findings comments, "It is very interesting that HRT has different effects on different types of breast cancer. One possible explanation for the findings is that certain types of breast cancer are more likely than others to be hormone receptive. Further research into this topic could greatly help our understanding of the biological mechanisms underlying the development of breast cancer."

In 2003, the million women study confirmed that post-menopausal women taking combination HRT were twice as likely as non-users to develop breast cancer and women taking oestrogen-only HRT had a 30 per cent greater risk than those who haven't taken HRT.

The increase in breast cancer risk starts within one to two years of beginning either form of HRT and increases the longer it is taken. As soon as HRT is stopped, the risk begins to fall and, after five years, is the same as for women who've never taken the drug. Combined oestrogen-progesterone HRT is usually prescribed for women who still have a uterus to avoid the increased risk of cancer of the uterus caused by oestrogen-only therapy. Women are advised to discuss their concerns with their doctor.

Breast asymmetry predicts breast cancer

Tue, 21 Mar 2006 02:17:37 PST

( from http://www.rxpgnews.com ) Women who go on to develop breast cancer tend to have breasts that are less symmetrical than women who don't develop the cancer. A study published today in Breast Cancer Research reveals that breast asymmetry could be a reliable independent predictor of breast cancer. The study found that the relative odds of developing breast cancer increased by 1.5 with each 100ml increase in breast asymmetry.

Diane Scutt from the University of Liverpool, UK and colleagues studied the mammograms of 252 women who did not have breast cancer at the time of the mammography, but later on developed the disease. The control group consisted of 252 women matched for age who underwent mammography at the same time, but did not develop breast cancer.

Scutt et al.'s results show that, at the time the mammography was done, women who went on to develop breast cancer had higher breast volume asymmetry than controls. The authors found that the relative odds of breast cancer increased by 1.5 for a 100ml increase in absolute breast volume asymmetry, after adjusting for other potential risk factors. They conclude that breast asymmetry is a significant independent predictor of breast cancer, and could be a reliable indicator of future breast disease.

Breast Screening Information Should be More Balanced

Sat, 04 Mar 2006 15:04:37 PST

( from http://www.rxpgnews.com ) The information sent to women about breast screening needs to be more balanced to ensure women are adequately informed about the benefits and harms, say researchers in this weeks BMJ.

Invitations to screening mammography play a central part in the process of obtaining informed consent, but conflict of interest exists for publicly funded screening, since organisers want a high uptake. Research also shows that women generally exaggerate the benefits and are unaware of the harms of screening.

The researchers examined mammography invitations from English speaking and Scandinavian countries with publicly funded screening to assess whether they provide sufficient information to enable women to make an informed decision.

Thirty invitations (97%) mentioned the main benefit of screening, a reduction in breast cancer mortality, but only seven gave the size of the benefit and none of them in a helpful way. In contrast, no invitation mentioned the major harm of screening, over-diagnosis and subsequent over-treatment.

Six invitations argued that screening leads to less invasive surgery and another four stated that it leads to simpler treatment. None of the invitations noted that research has shown that screening leads to increased use of surgery and radiotherapy arising from over-diagnosis.

Fifteen invitations (48%) recommended regular breast self examinations, despite doubts over their benefit and documented harms.

Although it is good news that the invitations often included an information pamphlet, the focus on the benefits of screening is problematic, say the authors. The most important harms, over-diagnosis and over-treatment, were not mentioned and other important harms were often either omitted or downplayed.

Two-thirds (68%) of invitations gave an appointment date, but they warn that this gives the impression that participation is a public duty. They believe that information material should convey the message that a decision not to attend is not irresponsible.

We believe that the information included with invitations should be more balanced, using absolute numbers to describe the likelihood of benefits and harms, and applying to the same time span if possible.

Furthermore, we suggest that the responsibility for the programmes should be separated from the responsibility for the information material and that consumer groups be involved in the process of developing balanced information material, they conclude.

An editorial on the UK breast screening programme outlines recent efforts to provide women with sufficient information to make an informed choice.

Malmö mammographic screening trial: Over-diagnosis in breast cancer screening

Sat, 04 Mar 2006 15:01:37 PST

( from http://www.rxpgnews.com ) Screening women for breast cancer could result in a 10% rate of over-diagnosis, finds a study published online by the BMJ today.

Although it is widely agreed that breast screening can reduce deaths, more discussion around this negative side effect of screening is needed, say the authors.

Researchers analysed the rate of over-diagnosis of breast cancer using data from a large breast screening trial conducted in Sweden between 1976 and 1986. Over-diagnosis is defined as cases that would never have come to clinical attention without screening.

They followed trial participants until December 2001, 15 years after the trial ended using national registries to track survival and detection of breast cancer.

Fifteen years after the end of the trial, the rate of over-diagnosis of breast cancer was 10% in women randomised to screening at age 55-69 years compared with an unscreened control group.

Although earlier studies on over-diagnosis have shown rates of up to 54%, a recent study suggests a much lower rate of 1%. But none of these studies were based on direct observations, like the present one, say the authors.

It is widely agreed that screening using mammography can reduce mortality in breast cancer. The rate of over-diagnosis is another issue to be considered in the ongoing discussion about clinical and public health implications of breast cancer screening, they conclude.

An editorial in this weeks BMJ discusses the UK breast screening programme and concludes that, although breast screening by mammography is far from perfect, it does save lives.

All benign papillary lesions of the breast should be surgically excised, new study suggests

Tue, 28 Feb 2006 15:27:37 PST

( from http://www.rxpgnews.com ) Certain breast lesions diagnosed as benign on core needle biopsy have cancer at surgical excision and thus should be removed, according to a study appearing in the March issue of Radiology.

"Our study shows that all papillary lesions of the breast should be surgically excised to avoid missing a cancer," said the study's lead author, Cecilia L. Mercado, M.D., assistant professor of radiology at New York University Medical Center in New York City.

Papillary lesions are benign growths in the duct of the breast. They comprise approximately 1 to 3 percent of all lesions sampled by core needle biopsies. Currently, the treatment of these lesions alternates between radiographic follow-up and surgical excision, and is often dependent upon physician recommendation.

"To date, the management of benign papillary lesions on core needle biopsy has been controversial and may be based on anecdotal evidence or small published studies," Dr. Mercado said. "No definite guidelines are published for management of these lesions."

While papillary lesions may be diagnosed as benign, they can harbor adjacent atypical ductal hyperplasia (ADH) a condition characterized by cells of unusual size, shape, and number in the lining of the milk ducts and ductal carcinoma in situ (DCIS), which are cancerous cells confined to the lining of the milk ducts. Left unchecked, both these conditions pose increased risk of future malignancy.

For the study, Dr. Mercado and colleagues reviewed the imaging and histologic follow-up findings in 42 patients diagnosed with benign papillary lesions after breast core needle biopsy. Forty-three biopsies were performed on the 42 patients. Of the 43 biopsies, 36 (84 percent) of the lesions were surgically removed, and seven (16 percent) received long-term imaging follow-up.

Upon surgical excision and follow-up, the diagnoses of nine of 42 patients (21.4 percent) were upgraded to ADH or DCIS. This is a much higher percentage than reported by previous studies.

"This is one of the largest series and shows statistically significant findings," Dr. Mercado said. "The results of our study revealed a considerable upgrade rate to either ADH or DCIS at core-needle biopsy. Therefore, all benign papillary lesions of the breast should be surgically excised, since a considerable number of atypical lesions and malignant lesions could be missed."

Eating less fat may lower breast-cancer risk

Wed, 08 Feb 2006 11:40:37 PST

( from http://www.rxpgnews.com ) Adopting a low-fat diet in later life and following such a regimen for nearly a decade does not appear to have a significant impact on reducing the overall risk of breast cancer, colorectal cancer or heart disease, according to a Women's Health Initiative study that involved nearly 50,000 postmenopausal women across the United States. The results of the federally funded dietary modification study will be published in a series of three papers two with lead authors at Fred Hutchinson Cancer Research Center and all three involving co-authors from the Hutchinson Center in the Feb. 8 issue of the Journal of the American Medical Association, or JAMA.

The study the first attempt to test the health impact of a low-fat diet in a randomized, controlled trial, considered the gold standard of clinical and public-health study design did, however, uncover some encouraging trends, according to Hutchinson Center biostatistician Ross L. Prentice, Ph.D., lead author of the JAMA paper that describes the impact of a low-fat diet on breast-cancer risk, one of the primary goals of the study.

"Women in the low-fat-diet group reduced their overall rate of breast cancer by about 9 percent as compared to the women who didn't change their eating patterns, but that difference was not statistically significant; it could have been due to chance. So at this point we're not able to say with certainty that a low-fat diet reduces the risk of breast cancer," said Prentice, member and former director of the Hutchinson Center's Public Health Sciences Division. A 9 percent reduction in breast-cancer incidence means that, out of 10,000 women, 42 in the low-fat-diet group and 45 in the comparison group developed breast cancer each year.

Prentice and colleagues did find, however, that a low-fat diet was associated with a statistically significant 15 percent reduction in estradiol, a form of blood estrogen that increases the risk of breast cancer.

Women in the low-fat group also experienced a 30 percent risk reduction for a certain subtype of breast cancer: tumors that were progesterone-receptor negative. "This finding provides an interesting hypothesis for further development and reinforces that breast cancer is multifaceted; it is not a single disease," Prentice said. PR-negative tumors, while relatively rare, are difficult to treat and associated with a higher mortality rate because they are unresponsive to hormone-blocking drugs such as tamoxifen.

Significant results were seen also among women in the low-fat-diet group who began the study with the highest baseline fat consumption and among women who most strictly adhered to the study's dietary-fat goals. Women in these categories experienced a 15 percent to 20 percent overall reduction in breast-cancer incidence.

"The bottom line is that changing to a low-fat diet may reduce breast-cancer risk, especially among women who have a relatively high-fat diet to begin with, but we don't view our data as strong enough at this time to make a broad recommendation that all women initiate a low-fat diet for that purpose," Prentice said. "Additional follow up with these women may yield a stronger, statistically significant conclusion."

With regard to colorectal cancer, the study did not reveal a reduction of cancer incidence overall, but it did show a modest 9 percent decrease in self-reported colon polyps a precursor to colon cancer among the women in the low-fat intervention group, according to Shirley A.A. Beresford, Ph.D., lead author of the paper describing the colorectal-cancer findings.

"It is important to remember that cancers often take decades to develop, and we may only be seeing the early stages of the impact of a low-fat diet intervention on the risk of colorectal cancer and other diseases," said Beresford, a member of the Hutchinson Center's Public Health Sciences Division and a professor of epidemiology at the University of Washington School of Public Health and Community Medicine. "The reduction in polyps suggests a possible reduction in colorectal-cancer risk could emerge over a longer time period." No significant reduction in heart disease emerged among the women in the low-fat intervention group, who achieved only a 2.4 percent reduction in low-density lipoprotein, or LDL, the so-called "bad" cholesterol, and a 3 percent lower rate of heart disease.

The study did, however, find trends toward reduction in heart-disease risk among the subset of women in the low-fat-diet group who made the greatest reduction in consumption of saturated fat and trans fat, both of which can raise the risk of heart disease because they increase production of LDL cholesterol.

"For heart-disease prevention, the data suggests that a greater emphasis on reduction of saturated and trans fats will be needed to have a major difference," Prentice said. Barbara V. Howard, Ph.D., president of MedStar Research Institute/Howard University in Washington, D.C., was the lead author of the heart-disease paper.

Nationally, 48,835 women between the ages of 50 and 79 participated in the study, including more than 1,000 from the Seattle area. Forty percent of the women were randomly assigned to follow a low-fat diet while 60 percent of the women served as a comparison group and thus maintained their usual eating habits. The women in both groups were followed for eight years.

Those in the low-fat group aimed to consume no more than 20 percent of daily calories from fat, and to eat at least five servings of vegetables and fruits and six or more servings of grains daily. To help reach this goal, the women met regularly in small groups with nutritionists to learn how to modify their behaviors to achieve and maintain this dietary change.

At the beginning of the study, the women's baseline fat consumption was between 35 percent and 38 percent of their daily calories. A year into the study, the women in the low-fat group got 24 percent of their energy from fat 11 percent fewer calories from fat as compared to the women who ate their usual diet and they maintained much of that difference throughout the study.

"This was a long-term, demanding study for the women in the low-fat group, and they did a marvelous job of trying to adhere to stringent dietary goals," Prentice said. "In spite of their efforts, we achieved only 70 percent of the difference in dietary habits between the two groups that we needed to get. If we'd achieved an even higher adherence rate, I believe the study's results would have been more dramatic," Prentice said.

"While the study didn't give us the results that some people were hoping for, it suggests that we're on the right track," he said. "Women can be confident that cutting back on fat and following the recommended Dietary Guidelines for Americans certainly won't hurt when it comes to maintaining a healthy lifestyle and preventing chronic disease."

Importantly, the low-fat, high-carbohydrate diet did not increase the risk of obesity, metabolic syndrome or diabetes.

Although the intervention phase of the study is complete, five years of data collection and follow-up are planned as well. "Additional follow-up with these women may yield a stronger, statistically significant conclusion," Prentice said. "The low-fat story is partly in, but it is not over yet."

A new site for cancer chemotherapy - Breast ducts?

Thu, 26 Jan 2006 23:47:37 PST

Dr. Sukumar

"We'd like to develop a treatment option for early breast cancers that minimizes disfigurement and spares normal tissues," says Sukumar who is the Barbara B. Rubenstein Professor of Oncology at Hopkins' Kimmel Cancer Center.

Standard treatments for early breast cancer, called ductal carcinoma in situ (DCIS), include radiation and surgery to remove the tumor via a lumpectomy or mastectomy. Chemotherapy, reserved for disease that has spread beyond the ducts, is not typically used to treat DCIS because conventional methods of delivering the drugs through an arm or chest vein would unnecessarily send the toxic chemicals coursing throughout the entire body.

"We found that, in animal models, injecting chemotherapy into the milk ducts confines most of the drug to the breasts, leaving other tissues unharmed," says Sukumar.

Building on observations made by her lab on rat models using drugs that block estrogen, Sukumar began tests in mouse models three years ago by using a chemotherapy drug called doxorubicin. The mice were bred to develop breast cancers that were genetically similar to treatment-resistant ones in humans.

First, researchers injected mice that had palpable tumors with a slow-release formulation of low dose doxorubicin directly into their mammary ducts. At the end of the observation period, this group had tumors less than half the size of those receiving the drug intravenously. Then, the scientists increased the drug dose, and, initially, tumors in both groups remained small. But that changed when 56 days later, tumors in the IV group ballooned - almost as large as control mice getting no treatment - while tumors in the intraductal group fared much better. Eight of 10 tumors in the intraductal group disappeared in 20 days. Some of the tumors grew back, but remained small compared with the IV group. At the end of the 91-day study period, four of the 10 tumors had not come back.

Sukumar also believes that injecting chemotherapy agents or prevention drugs like tamoxifen into the breast ducts could be one option for women at high risk for the disease.

To test this premise, her team injected doxorubicin via IV or intraductally into 40 mice bred to develop breast cancer. Control mice received injections of saline or no treatment. Mice receiving IV therapy were twice as likely to develop breast cancer (32 tumors in 170 mammary glands) than those receiving a single intraductal dose (13 tumors in 196 glands). Increasing the number of intraductal injections to two per mammary gland completely protected all 10 mice (100 glands) from developing the cancer while all intravenously treated mice succumbed to the disease. The scientists found similar results using a derivative of tamoxifen in rat models.

Phase I studies in breast cancer patients have begun to test the feasibility and safety of the procedure. Among the potential side effects that Sukumar's team, headed by Vered Stearns, M.D., breast cancer specialist at the Kimmel Cancer Center, will be studying in the trial are pain, inflammation, and changes in the structure of the duct network. Other areas for study include image-guided injections that could be rigged as "duct-detectors" to help pinpoint early lesions, as well as different chemotherapy drugs and dosing schedules.

More than 200,000 cases of breast cancer are diagnosed in the U.S. annually. DCIS accounts for 20 - 40 percent of these cases, according to researchers.

Minimal disfigurment treatment option for early breast cancers

Thu, 26 Jan 2006 01:38:37 PST

( from http://www.rxpgnews.com ) Johns Hopkins Kimmel Cancer Center researchers are studying whether delivering chemotherapy drugs directly to breast "plumbing" might make treatment of early breast cancer easier on the patient and at least as good as surgery or radiation.

A report on successful tests of intraductal therapy in rats and mice published in the January 15 issue of Cancer Research has paved the way for one of the first preliminary clinical trials in women with breast cancer, currently under way in women with breast cancer scheduled for a mastectomy at Johns Hopkins.

For more than a decade, researchers have been studying how to diagnose breast cancer earlier by extracting fluid from the vast network of tiny milking-producing ducts in the breast. The idea is based on the finding that most breast cancers sprout from cells lining the milk ducts. This same idea led Kimmel Cancer Center researcher Saraswati Sukumar, Ph.D., to explore the possibility of treating early breast cancers by using hair-thin catheters to inject chemotherapy through openings at the nipple directly into the place where they started - the milk ducts.

Sukumar likens the procedure to pouring detergent down the kitchen sink to rid the pipes of unwanted material. Because early breast cancers are less likely to have escaped the ducts, intraductal therapy may have at least as good a chance to cure as radiation or surgery.

"We'd like to develop a treatment option for early breast cancers that minimizes disfigurement and spares normal tissues," says Sukumar who is the Barbara B. Rubenstein Professor of Oncology at Hopkins' Kimmel Cancer Center.

Standard treatments for early breast cancer, called ductal carcinoma in situ (DCIS), include radiation and surgery to remove the tumor via a lumpectomy or mastectomy. Chemotherapy, reserved for disease that has spread beyond the ducts, is not typically used to treat DCIS because conventional methods of delivering the drugs through an arm or chest vein would unnecessarily send the toxic chemicals coursing throughout the entire body.

"We found that, in animal models, injecting chemotherapy into the milk ducts confines most of the drug to the breasts, leaving other tissues unharmed," says Sukumar.

Building on observations made by her lab on rat models using drugs that block estrogen, Sukumar began tests in mouse models three years ago by using a chemotherapy drug called doxorubicin. The mice were bred to develop breast cancers that were genetically similar to treatment-resistant ones in humans.

First, researchers injected mice that had palpable tumors with a slow-release formulation of low dose doxorubicin directly into their mammary ducts. At the end of the observation period, this group had tumors less than half the size of those receiving the drug intravenously. Then, the scientists increased the drug dose, and, initially, tumors in both groups remained small. But that changed when 56 days later, tumors in the IV group ballooned - almost as large as control mice getting no treatment - while tumors in the intraductal group fared much better. Eight of 10 tumors in the intraductal group disappeared in 20 days. Some of the tumors grew back, but remained small compared with the IV group. At the end of the 91-day study period, four of the 10 tumors had not come back.

Sukumar also believes that injecting chemotherapy agents or prevention drugs like tamoxifen into the breast ducts could be one option for women at high risk for the disease.

To test this premise, her team injected doxorubicin via IV or intraductally into 40 mice bred to develop breast cancer. Control mice received injections of saline or no treatment. Mice receiving IV therapy were twice as likely to develop breast cancer (32 tumors in 170 mammary glands) than those receiving a single intraductal dose (13 tumors in 196 glands). Increasing the number of intraductal injections to two per mammary gland completely protected all 10 mice (100 glands) from developing the cancer while all intravenously treated mice succumbed to the disease. The scientists found similar results using a derivative of tamoxifen in rat models.

Phase I studies in breast cancer patients have begun to test the feasibility and safety of the procedure. Among the potential side effects that Sukumar's team, headed by Vered Stearns, M.D., breast cancer specialist at the Kimmel Cancer Center, will be studying in the trial are pain, inflammation, and changes in the structure of the duct network. Other areas for study include image-guided injections that could be rigged as "duct-detectors" to help pinpoint early lesions, as well as different chemotherapy drugs and dosing schedules.

More than 200,000 cases of breast cancer are diagnosed in the U.S. annually. DCIS accounts for 20 - 40 percent of these cases, according to researchers.

Guidelines for International Breast Health and Cancer Control Released

Wed, 25 Jan 2006 16:26:37 PST

( from http://www.rxpgnews.com ) Specific recommendations for improving breast-health care and cancer treatment in countries with limited resources have been published by the Breast Health Global Initiative (BHGI), an international coalition of doctors, scientists, policy makers and advocates led by Fred Hutchinson Cancer Research Center and the Susan G. Komen Breast Cancer Foundation.

"The Guidelines for International Breast Health and Cancer Control" are published as a 122-page supplement in the January-February 2006 issue of The Breast Journal. The material is available free of charge on the Internet on the BHGI website at http://www.fhcrc.org/science/phs/bhgi/news/2006/updatedguidelines.html.

Benjamin O. Anderson, M.D., is chairman and director of BHGI, which he founded in 2002 to address the growing rate of breast cancer in developing nations and the need for such nations to provide more services to women.

"Many challenges in health care extend beyond the capacity of any one organization or sector to address effectively," he said. "This is especially true in a global world where traditional boundaries between what are 'public' and 'private' responsibilities have become blurred. The Guidelines for International Breast Health and Cancer Control is an example of what a collaborative, working global alliance can achieve."

Building on guidelines first published in 2003 to help developing nations find ways to make economically feasible and culturally appropriate care available to medically underserved women, "The Guidelines for International Breast Health and Cancer Control" expand and refine the earlier work by proposing an economically stratified approach to providing breast care based on available health-care resources, and a check-list format.

The BHGI Guidelines outline recommendations for breast health and cancer control in limited resource countries in four areas: Early Detection and Access to Care; Diagnosis and Pathology; Treatment and Allocation of Resources; and Health Care Systems and Public Policy. The Guidelines recommend, based on the country's resource level, what level of care and/or service to provide and evaluation goals. Four panels of BHGI experts developed the Guideline recommendations using an evidence-based consensus approach.

Diana Rowden, international director of the Komen Foundation, said the Guidelines "provide an essential, practical tool in the fight against breast cancer in limited- resource countries as well as a plan to expand and improve health-care systems. We're pleased to help make the Guidelines available to cancer researchers and advocates, health-care professionals, and policy makers around the world."

In an overview of the Guidelines published in The Breast Journal, Anderson and colleagues note that breast cancer is the most common cause of cancer-related deaths among women worldwide. Breast cancer is newly diagnosed in more than 1.1 million women annually; these cases represent 10 percent of all new cancer cases. Breast cancer deaths, at more than 410,000 annually, represent about 1.6 percent of all female deaths worldwide.

"Breast cancer is an urgent public-health problem in high-resource regions and is becoming an increasingly urgent problem in low-resource regions, where incidence rates have been increasing by up to 5 percent," the authors said.

Low-resource countries generally have not identified cancer as a priority health-care issue because infectious diseases are the predominant public-health threat, the study said. In these situations, cancer is most often treated when it is in its advanced stages, when treatment is most expensive and least successful. Cancer will become a greater health-care concern in low-resource countries as control of communicable diseases improves and life expectancy rises, the authors said.

While evidence-based breast-cancer guidelines exist for high-resource countries, they are of little value to poorer countries. "Current evidence about the value of earlier diagnosis and cost-effective diagnosis and treatment can nonetheless be applied to define evidence-based 'best practices with limited resources' for breast health care for use in countries where access to medical care is marginal, breast-cancer awareness is marginal and cultural barriers to effective care exist," the researchers reported. Developing guidelines for nations with limited resources "is a crucial step toward improving breast health care and breast cancer in these regions," the study said.

The 2005 Guidelines offer a stepwise, systematic approach to health-care improvement using a tiered system of resource allocation on four levels basic, limited, enhanced and maximal depending on a country's resources.

For example, in the area of breast-cancer early detection and access to care, the Guidelines suggest that countries with very basic health systems should educate women about performing breast self-examination to detect lumps. For countries with more but still-limited resources, the Guidelines recommend targeted outreach and education on clinical breast examination to women in at-risk groups, followed by ultrasound or mammography to confirm the discovery of suspected lumps. "We encourage ministries, cancer organizations, health professionals and patient networks across the world to actively engage in bridging the widening gap between what is and what could be," said Isabel Mortara, executive director of the International Union Against Cancer based in Geneva, Switzerland. UICC is an association of 270 cancer organizations in more than 80 countries, and a collaborating organization in the BHGI.

Rafael Bengoa, M.D., director of Health System Policies and Operations at the World Health Organization in Geneva, participated in the development of the Guidelines for Health Care Systems and Public Policy. He said, "In international development there are too many documents with 'should' recommendations and too few on 'how' to do things. Developing countries know the 'shoulds.' They want support with the 'how.' These Guidelines are about 'how' to handle cancer and resources more effectively."

Predictive Role of Somatostatin Receptor Scintigraphy (SRS) in Breast Cancer

Sun, 22 Jan 2006 15:04:37 PST

( from http://www.rxpgnews.com ) Innovative use of somatostatin receptor scintigraphy (SRS), a nuclear medicine imaging technique looking at how the body functions at the molecular level, may provide near immediate selection of breast cancer patients for endocrine therapy and offers a new tool in fighting the disease, according to a study published in the January Journal of Nuclear Medicine.

Breast cancer is the most common cancer among women and the second leading cause of cancer death in this country. About one in eight women will develop invasive breast cancer some time during her life, and more than 40,000 (1 in 33) of those die from the disease each year in the United States. Advanced or metastatic breast cancer patients receive either hormonal or chemotherapy treatment, depending on the hormone sensitivity of a woman's tumor. In some women, the female hormone estrogen promotes the growth of breast cancer cells. Endocrine or hormonal therapy removes the influence of estrogen on breast cancer cells, preventing the cancer cells from growing and spreading.

"Our technique allows a fast and accurate selection of breast cancer patients for hormonal treatment," explained Bieke Van Den Bossche, M.D., Ph.D., nuclear medicine department, Ghent University Hospital, Ghent, Belgium. "In routine practice, patients are assigned to hormonal treatmentor notdepending on the hormone receptor status of the primary tumor," said Van Den Bossche, co-author of "Early Prediction of Endocrine Therapy Effect in Advanced Breast Cancer Patients Using 99mTc-Depreotide Scintigraphy." She added, "With conventional imaging techniques, it takes at least three to six months to evaluate if the disease is regressing, stabilizing or progressing. Obviously, every day that a patient goes without efficient therapy is a day too many."

Hormonal treatment provides good results with minor side effects, but only patients who have tumors and metastases (spread) sensitive to hormones benefit from this type of treatment, she said. "Because only about one-third of breast cancer patients initially respond to endocrine therapy, there is a need for patient selection," said Van Den Bossche.

"The only technique used now to determine whether a patient's tumor is sensitive to hormonal therapy is examination of a piece of tumor tissue in a lab to see if hormone receptors are present," said Van Den Bossche, adding that this method has low accuracy. "With our technique, it is possible to take an imaging scan of the entire patientand treatment should be started when metastasis occursto evaluate if the tumor lesions are hormone sensitive and to assess what treatment would be efficient," she noted. "Our technique can assess hormone sensitivity with a whole-body imaging scan, which can be applied whenever needed in the course of the disease for all lesions at one time," she added.

While SRS is routinely used in nuclear medicine for diagnosis, Belgian and Italian researchers used SRS for therapy predictiona new and exciting field, noted Van Den Bossche. "We demonstrated the relationship between the expression of somatostatin receptors and the hormone sensitivity of human breast tumors along with use of somatostatin receptor imaging for selection of patients likely to respond to hormonal treatment," she said. By using 99mTc-labeled depreotide, which binds to somatostatin receptors and sends out flashes of light detected by a gamma camera, researchers were able to create an image of the presence of hormone-sensitive lesions in a patient's body. The study notes, "Sequential 99mTc-depreotide scintigraphy could allow for separation of responders and nonresponders immediately or as early as three weeks after initiation of treatment."

While these results come from an initial group of 20 patients, the team will continue to confirm the findings on a larger group of breast cancer patients, said Van Den Bossche. "This is necessary before a therapeutical consequence can be given to the SRS scan results. If the results are going to be in the same line, we could predict therapy response with an accuracy of 100 percent immediately or within three weeks after treatment initiation," she said.

Radioactive seeds might reduce the burden of treatment for women suffering from early-stage breast cancer

Wed, 04 Jan 2006 16:14:37 PST

( from http://www.rxpgnews.com ) Doctors in Canada are studying the effectiveness of permanent radiation seed implants following lumpectomy as an alternative to whole or partial breast irradiation for early-stage breast cancer patients, according to a study published in the January 1, 2006, issue of the International Journal of Radiation Oncology*Biology*Physics, the official journal of ASTRO, the American Society for Therapeutic Radiology and Oncology. This type of radiation would cut treatment time for certain patients from several weeks to one day.

For early stage breast cancer, women often undergo a lumpectomy to remove the tumor followed by radiation therapy to kill any cancer cells that may remain. Most women undergo external beam radiation, which is given every day, Monday through Friday, for six to eight weeks. Doctors have been experimenting with ways to shorten this treatment. One technique used by a growing number of radiation oncologists involves the use of temporary radiation implants. These radiation sources are delivered through a catheter into the breast, usually twice a day for one week.

In this study, the first of its kind in the world, doctors wanted to see if it was possible to use permanent implants, like what many men receive to treat prostate cancer, to combat the cancer with only one treatment. These implants, about the size of a grain of rice, would not be removed daily like with the temporary implants. Rather, the radioactive seeds would deliver radiation to the breast area for a number of weeks until they were no longer radioactive. The advantage over the temporary implants is that the patient only has to undergo one surgical procedure to receive the radiation, versus 10 treatments over one week for temporary implants.

The current treatment standard of lumpectomy followed by external beam radiation therapy is proven to keep the cancer from returning, but 38 percent of women develop significant toxicity, which can compromise their quality of life. According to early returns from the study, which began in May 2004, 44 patients have been treated successfully with the permanent implants. So far, none have evidence of their cancer returning and acute skin irritation is six times less frequent when compared to external beam radiation.

"The main motivation was to see if we could reduce the burden of treatment for women suffering from early-stage breast cancer," said Jean-Philippe Pignol, M.D., Ph.D., lead author of the study and radiation oncologist at Sunnybrook and Women's College Health Sciences Centre in Toronto, Ontario, Canada. "The seed implants reduce the treatment to a one-time event compared to the current standard of daily treatments over many weeks. The seeds also reduce the amount of radiation the normal breast tissue receives, which lessens the chance of the patient developing problems that affect their post-cancer quality of life. The great thing is that the patient can go home right after the procedure and live a normal life while receiving her radiation."

Higher levels of BCA2 are protective for regional breast cancer recurrence

Wed, 16 Nov 2005 21:01:38 PST

( from http://www.rxpgnews.com ) Researchers at Sunnybrook and Women's College Health Sciences Centre have found a new protein marker linked to positive outcome in patients with breast cancer.

The research published today in Cancer Research is the first to show that patients with high levels of the protein BCA2 are less likely to experience breast cancer re-occurrence than patients with low levels of BCA2.

"For the first time we have been able to show that the over-expression of BCA2 is a favorable factor in breast cancer in relation to occurrence of lymph node metastases and regional recurrence," says principle investigator Dr. Arun Seth, senior scientist in molecular and cellular biology research at Sunnybrook & Women's. "Higher levels of BCA2 are somewhat protective for regional recurrence."

Testing the effects of BCA2 expression in 1000 invasive breast tumor samples, researchers revealed that BCA2 is associated with the positive estrogen receptor, negative lymph node status and an increase in disease-free survival for regional recurrence.

Estrogen receptor (ER) positive invasive breast cancers in general have a better prognosis than ER-negative tumors and are less aggressive. In breast cancer where BCA2 and ER expression are co-regulated BCA2 might provide an alternative target for the treatment of hormone-refractory breast tumors.

BCA2, a novel RING type E3 ligase protein discovered by Seth's lab in 2000 and filed for a patent in the US in 2002, has an inherent autoubiquitination activity. Ubiquitin is a small protein that marks other proteins by attaching itself to them and directing them to the proteasome for degradation. The BCA2 mediated such ubiquitin modification of the specific cancer related proteins affect breast cancer progression.

"Now that we have determined that higher levels BCA2 are associated with a positive outcome, we are working to determine whether the BCA2 ligase functions as an oncogene in some tissues and as a tumor suppressor in others," says Seth who is also a professor at the University of Toronto. "Targeting the BCA2 mediated breakdown of tumor suppressors could provide a new therapy to block breast tumor growth."

The Canada Foundation for Innovation and the Ontario Innovation Trust, now the Ontario Research Fund - Research Infrastructure, funded the infrastructure for this research. The Canadian Institutes of Health Research and the Canadian Breast Cancer Research Alliance provided operating grants.

Sunnybrook and Women's College Health Sciences Centre is transforming health care through the dedication of its more than 10,000 staff members and volunteers. Specializing in women's health programs, caring for Canada's war veterans, conducting leading-edge research, and teaching the latest advances in healthcare through our affiliation with the University of Toronto, distinguishes Sunnybrook & Women's as one of the country's premier academic health sciences centres. Sunnybrook & Women's improves the lives of hundreds of thousands of people each year by caring for newborns, adults and the elderly, treating and preventing cancer, heart and circulation diseases, disorders of the brain, mind and nervous system, orthopaedic and arthritic conditions, and traumatic injuries.

Mammaglobin Blood Test Reliably Detects Breast Cancer Recurrence

Fri, 11 Nov 2005 00:21:38 PST

( from http://www.rxpgnews.com ) Researchers at Washington University School of Medicine in St. Louis have shown that mammaglobin, a protein secreted by breast tumor cells, can readily be detected in the blood serum of patients with metastatic breast cancer using an inexpensive, reliable clinical test.

"A test for mammaglobin holds significant promise for catching metastatic tumors early," says study co-author Timothy P. Fleming, Ph.D., research associate professor of surgery at the School of Medicine and a researcher with the Siteman Cancer Center. "Compared to the few other known biomarkers linked to breast cancer, mammaglobin is the best. The protein is found in breast tissue and is secreted by most breast tumors."

The study, published in Clinical Cancer Research, tested 56 women without breast cancer and 26 women with metastatic breast cancer. The women without breast cancer were found to have a steady, low level of mammaglobin in their blood. This baseline level was not affected by age, body mass index, menopausal status, race, smoking history or a family history of breast cancer.

In contrast, the women with metastatic breast cancer had on average much higher readings of mammaglobin than the baseline level, providing the potential to distinguish cancer-free patients from those with recurrent breast tumors.

In addition, about 80 percent of all breast cancers examined, regardless of the type of tumor or stage of development, tested strongly for mammaglobin while normal breast tissue had significantly less mammaglobin. Prostate, colon, lung and ovarian cancer tissues did not test positive for mammaglobin.

This study shows that mammaglobin levels in blood serum can be readily obtained with a test called ELISA, an inexpensive clinical test often used to measure protein levels in fluids.

The test detected even very low concentrations of mammaglobin in blood serum and maintained accuracy over a 1,000-fold increase of mammaglobin concentration. Serum samples subjected to repeated freezing and thawing or stored frozen for a year tested just as effectively as fresh samples, indicating no potential problems with sample storage.

"Originally, we identified the gene that produces mammaglobin because it is activated in breast cancer relative to non-malignant breast cells," says study co-author Watson, associate professor of pathology and immunology and director of the Multiplexed Gene Analysis Core and Tissue Procurement Core at Siteman. "It's exciting to be a part of the research developments surrounding mammaglobin," Fleming says. Next, we are planning to work on high-throughput techniques to test our mammaglobin blood test in a much larger study."

HERA (HERceptin Adjuvant) Breast Cancer Trial Published in NEJM

Fri, 21 Oct 2005 16:00:38 PST

( from http://www.rxpgnews.com ) Today, the New England Journal of Medicine (NEJM) reports that the administration of Herceptin® (trastuzumab) following standard chemotherapy significantly reduces the risk of disease recurrence for women with early-stage HER2-positive breast cancer by 46%.

The interim results from the international HERA (HERceptin Adjuvant) study provide new hope in the fight against HER2-positive breast cancer, a more aggressive form of the disease affecting approximately 20 30% of women with breast cancer . The HERA study is one of the largest breast cancer trials ever carried out, with more than 5,000 patients in 39 countries. The study allowed the use of a wide range of chemotherapy regimens before treatment with Herceptin, making the results relevant to many parts of the world.

Dr Martine Piccart, lead investigator of the HERA study and Chair of the Breast International Group (BIG), commented, "Breast cancer is a serious and sometimes life-threatening disease, but with appropriate and timely treatment in the early stages, many women can improve their chances of long-term survival. For women with early-stage HER2-positive breast cancer, results from the HERA study provide some much needed optimism. The study showed that Herceptin, a drug designed specifically for HER2-positive breast cancer, can remarkably reduce the risk of cancer returning." Dr. Piccart added, "I can't stress enough how crucial it is that all patients' breast tumours are tested appropriately at initial diagnosis, and if patients are HER2-positive, that they have access to Herceptin."

Results from a joint interim analysis of over 3,000 patients from two North American trials provided similar remarkable results for Herceptin in early-stage HER2-positive breast cancer, and were also published in the NEJM today. These data, at a median follow-up of two years, show that Herceptin in combination with a specific chemotherapy regimen provided a 52% reduction in risk of cancer coming back as well as a 33% reduction in risk of death.

The strength of the results from the HERA study has influenced medical and regulatory organizations around the world to act urgently to ensure access to Herceptin for early-stage HER2-positive breast cancer patients. Several countries are already developing clinical guidelines and committing funding to allow eligible patients faster access, prior to license.

About the HERA study

HERA, conducted by the Breast International Group (BIG) and Roche , is one of the largest adjuvant studies ever carried out among breast cancer patients; enrolment to the trial began in December 2001, and nearly 5,100 HER2-positive patients were enrolled at 480 sites in 39 countries across the world. HERA is a randomised trial, which, following standard adjuvant systemic chemotherapy and radiotherapy (if applicable), evaluates observation versus Herceptin every three weeks for 12 months or 24 months in women with early-stage HER2-positive breast cancer. The HERA study allowed for the use of a wide range of chemotherapy regimens, and both lymph node-positive and lymph node-negative patients were eligible for entry into the trial.

According to the interim analysis, the primary efficacy endpoint was met, showing that in both 12- and 24-month arms, patients who received Herceptin had a statistically significant improvement in disease-free survival (the length of time after treatment during which no disease is found). At a median follow-up of one year, the secondary endpoint of overall survival had not reached statistical significance, but an improvement in overall survival is also possible as the data mature.

The NEJM article provides the results of the comparison between 12 months of Herceptin versus observation, but not a comparison of 12 months versus 24 months treatment duration. The trial will continue to assess this comparison and data are expected in 2008.

All study data are managed by a Brussels-based BIG member group, the Breast European Adjuvant Studies Team (BrEAST), with independent statistical analysis carried out in Boston and Scotland by the non-profit research organization, Frontier Science. The HERA study also has an external Independent Data Monitoring Committee (IDMC) that regularly reviews safety data. No safety concerns were raised by the IDMC, and the incidence of congestive heart failure was very low (0.5% in the Herceptin arm vs. 0% in the observation arm). Patients in this study will continue to be followed for any side effects for up to ten years.

High Risk African American Women may Benefit from Breast Cancer Gene Testings

Wed, 19 Oct 2005 20:17:38 PST

( from http://www.rxpgnews.com ) African American women at high-risk of breast cancer have genetic mutations that would make genetic testing feasible, according to a study in the October 19 issue of JAMA.

Because of recent advances in the understanding of breast cancer risk factors and the promise of prevention, women from high-risk families are encouraged to consider genetic testing to quantify their risk, according to background information in the article. An estimated 5 percent to 10 percent of breast cancer cases occur in individuals with inherited mutations in breast cancer susceptibility genes. Germline mutations in BRCA1 and BRCA2 are by far the most common and account for 80 percent to 90 percent of families containing multiple cases of breast and ovarian cancer. The proportion of breast cancer attributed to mutations in BRCA1 or BRCA2 has varied widely among different studies and different ethnic groups. Of note, one of the largest ethnic minorities in the United States, the African American population, remains understudied, despite having a proportionately higher incidence of early-onset breast cancer. Many of the risk-assessment tools used in cancer risk clinics, such as the BRCAPRO statistical model, were developed based on mutation rates observed primarily in Ashkenazi Jewish and other white women of European descent.

Rita Nanda, M.D., of the University of Chicago Medical Center, Chicago, and colleagues conducted a study to characterize the clinical predictors of BRCA1 and BRCA2 mutations among high-risk individuals of European and African ancestry, highlighting the similarities and differences.

The study included a comparative analysis of families (white, Ashkenazi Jewish, African American, Hispanic, Asian) with 2 or more cases of breast and/or ovarian cancer among first- and second-degree relatives. Families were identified at U.S. sites between February 1992 and May 2003; in each family, the individual with the highest probability of being a mutation carrier was genetically tested.

The researchers found that the mutation spectrum was vastly different between families of African and European ancestry. Compared with non-Hispanic, non-Jewish whites, African Americans had a lower rate of deleterious BRCA1 and BRCA2 mutations but a higher rate of sequence variations (27.9 percent vs. 46.2 percent and 44.2 percent vs. 11.5 percent). Deleterious mutations in BRCA1 and BRCA2 were highest for Ashkenazi Jewish families (69.0 percent). Early age at diagnosis of breast cancer and number of first- and second-degree relatives with breast and ovarian cancer were significantly associated with an increased likelihood of carrying a BRCA1 or BRCA2 mutation. In discriminating between mutation carriers, BRCAPRO performed as well in African American families as it did in white and Jewish families.

"BRCA1 and BRCA2 mutations do occur with appreciable frequency in high-risk families of African ancestry, with 28 percent testing positive for a deleterious mutation in 1 of these genes, a rate consistent with other clinic-based studies in the United States," the authors write.

"Our data support the use of personal and family history of breast cancer, ovarian cancer, or both in making clinical decisions and identifying individuals who are likely to benefit from genetic counseling. Certain family characteristics-most notably the number of breast cancer cases among first- and second-degree relatives and the mean age at diagnosis of breast cancer-are associated with the likelihood of carrying a deleterious mutation among African Americans, as has previously been observed in white and Ashkenazi Jewish families," the researchers write.

"Our observations underscore the need for large, collaborative studies to systematically validate the role of genetic testing, the use of risk prediction models, and the role of risk-reducing strategies in improving health outcomes for individuals of African ancestry," the authors conclude.

Black breast cancer patients have shorter survival - Reasons

Sat, 15 Oct 2005 19:45:38 PST

( from http://www.rxpgnews.com ) Although breast cancer survival has improved over the last 30 years, disparities in breast cancer survival between blacks and whites have not declined and remain sizeable, according to background information in the article. The 5-year U.S. survival rates in 1995-2000 for black and white breast cancer patients were 75 percent and 89 percent, respectively. Although several causes have been identified, such as advanced cancer stage, lack of access to medical care, inferior treatment, and lower socioeconomic status (SES), not all reasons for this disparity are understood.

C. Martin Tammemagi, Ph.D., of Brock University, St. Catharines, Ontario, Canada and colleagues evaluated data from breast cancer patients to evaluate the associations between adverse comorbidities (co-existing illnesses) and racial survival disparity. A group of patients (n = 906) from the Henry Ford Health System (a large comprehensive health system in Detroit) were followed up for a median of 10 years. Patients included 264 black (29.1 percent) women and 642 white (70.9 percent) women diagnosed as having breast cancer between 1985 and 1990. Detailed comorbidity data (268 comorbidities) and study data were abstracted from various medical records, databases and registries.

A total of 159 blacks (61.9 percent) and 317 whites (50.4 percent) died. Overall, 62.4 percent of deaths were attributed to competing causes. Proportionately more blacks than whites died of breast cancer (64 [24.9 percent] vs. 115 [18.3 percent]) and of competing causes (95 [37.0 percent] vs. 202 [32.1 percent]). Compared with whites, blacks had shorter overall survival (34 percent more likely), breast cancer-specific survival (47 percent more likely to have shorter survival), and competing-causes survival (27 percent more likely to have shorter survival). One or more comorbidities were reported in 221 blacks (86 percent) and 407 whites (65.7 percent). A total of 77 adverse comorbidities were associated with reduced survival. Comorbidity count was associated with all-cause and competing-causes survival but was not associated with recurrence/progression or breast cancer-specific survival. Comparisons of unadjusted and comorbidity-adjusted hazard ratios indicated that comorbidity explained 49.1 percent of all-cause and 76.7 percent of competing-causes survival disparity. Diabetes and hypertension were particularly important in explaining disparity.

"Our findings indicate that control of comorbidity may be an important way of improving the survival of black breast cancer patients and reducing racial disparity. That comorbidity explained more than 40 percent of the survival disparity in patients younger than 70 years indicates that effective management of comorbidity has the potential to lead to a substantial increase in person-years of life gained. Control of just 2 comorbidities, diabetes and hypertension, could have a major beneficial impact," the authors conclude.

Role of stem cell niche in breast cancer development

Tue, 04 Oct 2005 19:55:38 PST

( from http://www.rxpgnews.com ) Researchers at Georgetowns Lombardi Comprehensive Cancer Center have found that the onset of breast cancer may be due to defects in somatic adult stem cell niches that exist long before tumors develop.

The research, published in the October 2005 issue of Tissue and Cell, is the first to examine the highly specialized microenvironment, termed the stem cell niche, which surrounds adult stem cells, and its role in breast cancer development. These niches are key regulators of stem cell activity in mammary tissue, and defects that develop in these groups of cells can give rise to breast cancer.
This study helps us understand adult stem cells differently than we previously did. Particularly, when looking for the causes of breast cancer, we must take into account the stem cell as well as the environment that surrounds it, said Robert Dickson, Ph.D., co-author of the paper and co-director of the breast cancer program at the Lombardi Comprehensive Cancer Center.

The study used genetically engineered mice as models of ductal or lobular breast cancer that is caused by overproduction of certain proteins. These proteins (c-Myc and TGF-alpha) exist naturally in the body, but when produced in excess in mammary tissue cells, breast cancer can develop.

Gloria Chepko, Ph.D., a postdoctoral fellow and the papers lead author, built on previous research results that demonstrated the existence of five different types of cells in normal breast tissue. Two of the cell types are stem cell-like and give rise to the other three. For the present study, she devised a method to identify all the cell types at low magnification, allowing more cells to be counted. The arrangements form repeating units called stem cell niches and provide nest-like microenvironments that house the adult stem cells and their immediate daughter cells.

In the mice that expressed excess amounts of either of the cancer-producing proteins, the size of the cell populations were significantly changed relative to each other. The order of the cell arrangements was disrupted in the stem cell niches of mice with breast cancer. These results provided the first evidence that each cell population may play a different role in the development of breast cancer and that the environment in which a cell grows can influence its chance of becoming cancerous.

Breast Implants Do Not Cause Breast Cancer Recurrence In Mastectomy

Wed, 28 Sep 2005 13:16:38 PST

( from http://www.rxpgnews.com ) Women interested in immediate breast reconstruction after mastectomy should not worry that their implants could cause, hinder detection of, or affect treatment of cancer recurrence, according to a study presented today at the American Society of Plastic Surgeons (ASPS) Plastic Surgery 2005 conference in Chicago.

For women contemplating immediate breast reconstruction, there is a lot of information being presented to them. As plastic surgeons, we want to help our patients feel better about their bodies without risking their safety and long-term health, said Andrea Pusic, MD, ASPS Member Surgeon and co-author of the study. It is important for us to provide them with hard facts that show an implant does not increase the chance that their cancer could recur, delay the diagnosis of a recurrence or affect the outcome.

In the study, 309 women who had immediate breast reconstruction with an implant were compared, on the basis of age and stage of disease, to a group of 309 women who had mastectomy without reconstruction. The incidence of local breast cancer recurrence in reconstructed patients (6.8 percent) was not significantly different from non-reconstructed patients (8.1 percent). In addition, the implants did not hinder early detection of recurrence. Ninety-five percent of recurrences were initially detected by physical examination of the breast during regular check-ups with their plastic surgeon or oncologist. Five percent of recurrences were detected through a computer-assisted tomography (CT) or bone scan.

The treatment for recurrence was not affected by the implants and did not generally require removal of the implants. In the study, only three of the 21 patients who experienced a recurrence had their implants removed after treatment, and two of those patients specifically requested their implants be removed for personal reasons.

We are pleased to report that treating breast cancer recurrence rarely requires the removal of patients implants, said Dr. Pusic. This is reassuring information for women who choose to have implant-based breast reconstruction.

In 2004, almost 63,000 women had breast reconstruction after mastectomy, according to ASPS statistics. The American Cancer Society estimates 211,240 new cases of invasive breast cancer will occur in 2005 among women in the United States and more than 40,000 women will die from the disease.

Cancer Screening Useful in Breast Reduction Surgery Patients

Wed, 28 Sep 2005 13:06:38 PST

( from http://www.rxpgnews.com ) Twelve percent of breast reduction patients may have abnormal pathologies placing them at an increased risk of developing breast cancer, according to a study presented today at the American Society of Plastic Surgeons (ASPS) Plastic Surgery 2005 conference in Chicago. In addition, the authors found it more cost effective to screen breast reduction patients of all ages, not just those over 40, the age when routine screening mammography is recommended.

Plastic surgeons who perform breast reductions routinely have the removed tissue tested for abnormalities. While the screening of each patient may detect breast cancer early, it also escalates the overall cost.

We are in a time in medicine when cost is an important factor. Pressure from insurance companies and general administrators often force physicians to consider the cost of care when treating a patient, said Kristin Stueber, MD, ASPS Member Surgeon and co-author of the study. However, detecting breast cancer as early as possible reduces treatment costs and saves lives. In the end, we found that although it may cost more up-front to screen each breast reduction patient for cancer, we saved money and helped patients to get treatment sooner.

In the study, 12 percent of the 300 patients tested, ranging from 14 to 73 years old, had abnormal pathology reports indicating either a premalignant lesion or a lesion that puts the patient at an increased risk of developing breast cancer. Of those with an abnormal outcome, 28 percent were deemed moderate or high risk, placing them at a significantly higher threat than the general population for developing breast cancer. Two of the 10 high-risk patients were less than 40 years old. Any patient with an abnormal test was referred to a comprehensive breast center to watch for indications of breast cancer.

Based on the study of 300 patients where pathologic examination of each patients breast tissue was $381.72, there could have been a savings of $81,688 by only testing women above the age of 40, who equaled less than 29 percent of the patients. However, selective testing would have missed two potential cases of breast cancer.

If we were to limit our pathologic examination of breast tissue to breast reduction patients older than 40, we would fail to identify 20 percent of moderate to high risk pathology, which is simply not an acceptable risk, said Dr. Stueber. Besides the potential cost savings in testing, the cost for treating a cancer patient down the road is certainly more than any savings we could produce in the short term.

More than 105,500 women had breast reduction surgery in 2004, according to ASPS statistics. Applying the findings of this study to last years numbers, if the medical community only tested women above the age of 40, it would have missed 633 cases of moderate to high risk breast cancer.

Breast cancer is 90 percent curable when discovered early. An estimated 211,240 new invasive cases of breast cancer are expected to occur in 2005 among women in the United States, according to the American Cancer Society. This year, more than 40,000 women are expected to die from the disease.

Digital mammography better for many women

Mon, 19 Sep 2005 12:41:38 PST

( from http://www.rxpgnews.com ) A new study that enrolled nearly 50,000 women has revealed that digital mammography can detect breast cancer better than conventional film-based mammography in certain groups of women.

Overall, the study showed that conventional film mammography and digital mammography were equally effective. However, digital mammography performed better for the following groups: women under 50, women who are premenopausal and perimenopausal and women with dense breasts. The total of these groups represents at least 50% of the general population of women.

Physicians from 33 sites in the U.S. and Canada participated in DMIST (Digital Mammographic Imaging Screening Trial). Investigators at Washington University School of Medicine in St. Louis screened the largest cohort of volunteers in the study, enrolling more than 3,300 patients at the Joanne Knight Breast Health Center, which is affiliated with Barnes-Jewish Hospital and the Siteman Cancer Center.

Scientists announced the results of DMIST today at the fall meeting of American College of Radiology Imaging Network (ACRIN). It is simultaneously being published online by The New England Journal of Medicine. The National Cancer Institute funded the DMIST trial.

"From the patient's perspective, the digital mammogram experience is the same as a conventional mammogram," says Dione Farria, M.D., assistant professor of radiology at Mallinckrodt Institute of Radiology and principal investigator for the DMIST study site at Washington University Medical Center. Both technologies require X-rays and breast compression to obtain an image.

"Unlike conventional film mammography, though, digital mammography stores a digital image of the breast in a computer," Farria says. "This allows radiologists to use computer software to manipulate the images in order to optimize their ability to evaluate the breast tissue."

Farria notes that the DMIST results do not mean that women who have had conventional mammograms need to go back to their doctors immediately and request a digital mammogram." Since only eight percent of mammography units in the United States are digital units, it will not be possible for all women to receive digital mammograms in the near future," she says. "Furthermore, the study showed that digital mammograms did not offer an advantage to all women."

Researchers emphasize that it is important for women to continue having routine screening mammograms, because it has been scientifically proven that conventional mammography saves lives by detecting breast cancers earlier.

"Whether a facility has digital or conventional film mammography is only one factor to consider when choosing a mammography facility," Farria says. "The expertise of the radiologists who read the mammograms and the skill of the technologists are probably equally -- if not more -- important. While it is highly likely that we are going to see a transition from film to digital mammography, several factors will influence the speed of this change. "

Cost is a potential limiting factor in expanding the use of digital mammography. While a traditional mammography unit typically costs about $75,000-100,000, digital units with the required computer workstation may costs 3- 5 times more.

Since digital mammography is significantly more expensive than conventional mammography, DMIST investigators plan to conduct an analysis of the new technology in the context of its cost-effectiveness. Researchers are also concerned about the ability of small mammography facilities to raise the capital necessary to convert to digital technology.

In women, breast cancer is the most common malignancy and the second leading cause of cancer death. Last year, there were more than 215,000 new cases of invasive breast cancer and over 40,000 breast cancer-related deaths in the United States. In the state of Missouri in 2004, the American Cancer Society estimates that 4,680 women were diagnosed with breast cancer and 870 women died from breast cancer.

BCIRG Study Showed Reduction in the Risk of Disease Recurrence in Early-Stage HER2-Positive Breast Cancer

Wed, 14 Sep 2005 21:27:38 PST

( from http://www.rxpgnews.com ) Genentech, Inc. (NYSE: DNA) today announced that a planned interim analysis of a Phase III trial of Herceptin® (Trastuzumab) plus chemotherapy in the adjuvant setting showed a significant reduction in the risk of disease recurrence in women with early-stage (or cancer that has not spread beyond the breast and associated lymph nodes) human epidermal growth factor receptor 2 (HER2)- positive breast cancer. The international study was supported by sanofi-aventis and Genentech, and conducted by the Breast Cancer International Research Group (BCIRG), who plans to submit the data to the San Antonio Breast Cancer Symposium (SABCS), December 8 to 11, 2005.

The trial evaluated three regimens as adjuvant therapy following initial treatment with surgery:

* doxorubicin and cyclophosphamide (AC) followed by Herceptin plus Taxotere® (docetaxel) chemotherapy (experimental arm)
* Taxotere and carboplatin chemotherapies plus Herceptin (TCH) (experimental arm)
* AC followed by Taxotere alone (control arm)

This study differs from the two U.S. cooperative group trials presented at this years American Society of Clinical Oncology (ASCO) meeting in that the BCIRG study included a novel regimen of Herceptin plus chemotherapy (TCH), enrolled both node-positive and node-negative patients, included Taxotere, and determined HER2 status by FISH (fluorescent in situ hybridization) testing.

"We are excited that the fourth Phase III trial of Herceptin plus chemotherapy showed an improvement in disease-free survival for women with early-stage HER2-positive breast cancer," said Susan Desmond-Hellmann, M.D., M.P.H., Genentech president, product development. "Based on the strength of the data from the two U.S. adjuvant studies presented at this years ASCO meeting, we continue to anticipate filing a supplemental Biologics License Application (sBLA) for Herceptin in the adjuvant setting based on data from the U.S. studies in the first quarter of 2006."

This study showed that adding Herceptin to Taxotere following AC chemotherapy or adding Herceptin to Taxotere and carboplatin chemotherapies resulted in improved disease-free survival compared to chemotherapy alone, which is consistent with the results obtained from a joint analysis of the two U.S. cooperative group studies (NSABP and NCCTG).

The reduction in the risk of disease recurrence, the primary endpoint of the study, was 51 percent (95 percent confidence interval of 35 percent to 63 percent) in the arm adding Herceptin to Taxotere following AC and 39 percent (95 percent confidence interval of 21 percent to 53 percent) in the TCH arm. These reductions are statistically significant and crossed the predefined efficacy boundary.

These findings resulted from a planned interim analysis of 3,222 patients after approximately one-third of the required number of relapses had occurred. The comparison of efficacy data from the two Herceptin-containing regimens is not sufficiently mature to reliably determine differences at this time. The number of events required for analysis of the secondary endpoint of overall survival has not yet been reached; these data will be available at a later date.

The rate of clinically significant cardiac events, including congestive heart failure (weakening of the heart muscle), in the TCH arm was the same as the control arm of AC/Taxotere (1.2 percent in each arm). Cardiac events occurred at a rate of 2.3 percent in the AC/Taxotere/Herceptin arm. This study has an Independent Data Monitoring Committee (IDMC) that reviewed data from the studies, including cardiac safety data. The IDMC monitored safety data on a regular basis and the incidence of cardiac safety in the Herceptin plus chemotherapy arm was deemed acceptable by the DMC.

"This is the first time in HER2-positive breast cancer research that we have demonstrated that a novel Herceptin-containing regimen without anthracyclines is superior to one of the regimens containing anthracyclines commonly used today in breast cancer," said Dennis Slamon, M.D., Co-Chair of the BCIRG study and Director of Clinical and Translational Research at UCLA's Jonsson Comprehensive Cancer Center.

The BCIRG study enrolled its first patient in March 2001, and has randomized a total of 3,222 patients. The study is closed to accrual and the BCIRG cooperative group will continue to monitor patients for longer-term data.

About the Herceptin Adjuvant Clinical Trial Program
In addition to the BCIRG study, interim analyses of three additional adjuvant studies reported earlier this year showed that the addition of Herceptin to a chemotherapy regimen increased disease-free survival for women with early-stage HER2-positive breast cancer.

In April 2005, Genentech announced that a joint interim analysis of two U.S. cooperative group Phase III trials showed an improvement in the primary endpoint of disease-free survival and in the secondary endpoint of overall survival. The trials compared Herceptin plus paclitaxel chemotherapy to paclitaxel chemotherapy alone as adjuvant therapy following initial treatment with surgery for women with early-stage HER2-positive breast cancer.

An interim analysis from a third adjuvant trial called HERA, which was conducted internationally by Roche and Breast International Group (BIG), also showed that treatment with Herceptin plus chemotherapy improved disease-free survival.

Herceptin is a targeted therapeutic antibody treatment for women with HER2-positive metastatic breast cancer, an especially aggressive form of the disease that affects approximately one-fourth of women with breast cancer. Special testing is required to identify women who are HER2-positive and candidates for treatment with Herceptin.

Herceptin received U.S. Food and Drug Administration (FDA) approval in September 1998 for use in women with metastatic breast cancer who have tumors that overexpress the HER2 protein. It is indicated for weekly treatment of patients both as first-line therapy in combination with paclitaxel and as a single agent in second- and third-line therapy. Herceptin is marketed in the United States by Genentech, in Japan by Chugai, and internationally by Roche.

In clinical trials, Herceptin has shown a survival benefit when used in combination with chemotherapy. In December 2001, Genentech received FDA approval to include data that showed a 24 percent increase in median overall survival for women with HER2-positive metastatic breast cancer treated initially with Herceptin and chemotherapy compared to chemotherapy alone (median 25.1 months compared to 20.3 months).

Herceptin therapy does involve risks. Serious side effects have occurred in patients treated with Herceptin in metastatic breast cancer. Herceptin administration can result in the development of ventricular dysfunction and cardiac failure. Severe hypersensitivity reactions (including anaphylaxis), infusion reactions, and pulmonary events have been infrequently reported. Rarely, these were fatal.

Recently, Genentech issued a letter to healthcare providers explaining the cardiac monitoring guidelines under which the two U.S. cooperative group trials of Herceptin in the adjuvant setting were conducted.

Serious reactions were treated by discontinuing Herceptin and administering supportive therapy. In clinical trials, the incidence and severity of cardiac dysfunction was highest in patients receiving Herceptin with anthracycline and cyclophosphamide (AC). Most patients responded to medical therapy, including discontinuation of Herceptin. However, some patients were successfully managed while continuing Herceptin therapy. Patients receiving Herceptin should be monitored for deteriorating cardiac function.

In clinical trials, approximately 40 percent of patients experienced symptoms such as chills and fever during the first infusion. These and other symptoms, including nausea, vomiting, and pain, occurred infrequently with subsequent infusions. In clinical trials, the incidence of moderate to severe neutropenia and of febrile neutropenia were higher in patients receiving Herceptin in combination with myelosuppressive chemotherapy as compared to those receiving chemotherapy alone. There was an increased incidence of anemia leukopenia, diarrhea, and infection when Herceptin was used in combination with chemotherapy.

According to the American Cancer Society, an estimated 211,240 women will be diagnosed with breast cancer and approximately 40,000 women will die of the disease in the United States in 2005. Breast cancer is the most common cause of cancer among women in the United States and a woman is diagnosed with breast cancer in the United States every three minutes.

Genentech is committed to changing the way cancer is treated by establishing a broad oncology portfolio of innovative, targeted therapies with the goal of improving patients lives. The company is the leading provider of anti-tumor therapeutics in the United States. Genentech is leading clinical development programs for Rituxan® (Rituximab), Herceptin® (Trastuzumab), Avastin® (bevacizumab), and Tarceva® (erlotinib), and markets all four products in the United States, either alone (Avastin and Herceptin) or with Biogen Idec Inc. (Rituxan) or OSI Pharmaceuticals, Inc. (Tarceva). Genentech has licensed Rituxan, Herceptin, and Avastin to Roche for sale by the Roche Group outside of the United States.

The company has a robust pipeline of potential oncology therapies with a focus on four key areas: angiogenesis, apoptosis (i.e., programmed cell death), the HER pathway, and B-cell biology. A therapeutic antibody directed at the HER pathway is currently in Phase II trials and in early development are a small molecule directed at the hedgehog pathway, a therapy targeting apoptosis, and a humanized anti-CD20 antibody for hematology/oncology indications.