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Last Updated: Oct 11, 2012 - 10:22:56 PM
Breast Cancer Channel

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Latest Research : Cancer : Breast Cancer

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High Risk African American Women may Benefit from Breast Cancer Gene Testings

Oct 19, 2005 - 8:18:00 PM
"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"

[RxPG] 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.

Publication: October 19 issue of JAMA
On the web: JAMA . 2005;294:1925-1933 

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