'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 one of these genes.'

An estimated 5-10 percent of breast cancer cases occur in individuals with inherited genetic mutations, according to the article. The most common -- germline mutations in BRCA1 and BRCA2 -- are present in 80-90 percent of families containing multiple cases of breast and ovarian cancer.

Clinical Predictors

Despite having a proportionately higher incidence of early onset breast cancer, African American women as a group have been understudied in this regard. 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, MD, of the University of Chicago Medical Center 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 white, Ashkenazi Jewish, African American, Hispanic and Asian families with two or more cases of breast or ovarian cancer among first- and second-degree relatives. In each family, the individual with the highest probability of being a mutation carrier was genetically tested.

Mutation Spectrum

The mutation spectrum was vastly different between families of African and European ancestry, the researchers found. Compared with non-Hispanic, non-Jewish whites, African Americans had a lower rate of deleterious BRCA1 and BRCA2 mutations (27.9 percent vs. 46.2 percent), but a higher rate of sequence variations (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, as well as the number of first- and second-degree relatives with breast or ovarian cancer, correlated significantly 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.

Role of Genetic Testing

"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 one of these genes, a rate consistent with other clinic-based studies in the United States," note the authors.

"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," they add.

"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 authors point out.

"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," they conclude.