Testing for hereditary breast and ovarian cancer in the southeastern United States.

Interest in familial breast cancer is high among surgeons and their female patients. Both physicians and patients may misinterpret the significance of a familial clustering of breast cancer cases. The occurrence of breast cancer in more than one family member may cause concern about hereditary factors. Conversely, some women may underestimate their breast cancer risk because they have no affected relatives. Overall, women tend to overestimate the likelihood of breast cancer and exaggerate the significance of family history. 1,2 It is possible that misperceptions lead to inappropriate anxiety on the part of patients and unnecessary medical interventions by their physicians. Hereditary breast cancer is a rare syndrome in most populations of women seen in the United States. The majority of breast cancer cases occur in the absence of a significant family history. Twenty percent of women presenting with primary breast cancer have one or more relatives with a history of the disease. A smaller fraction of affected women have a family history consistent with a genetic cause. 3 However, in some of these rare families, occurrence of breast cancer can be linked to one of two susceptibility genes, BRCA1 or BRCA2. 4,5 Certain mutations in either of these two genes can be inherited as an autosomal dominant trait passed on average in the germline to 50% of a single carrier’s offspring (either father or mother). For women who inherit a mutant allele of BRCA1 or BRCA2, the lifetime risk of getting breast cancer (genetic penetrance) is estimated at 50% to 80%. 6–9 For ovarian cancer, a much less common disease, the penetrance of BRCA1 is probably less than 40%. For BRCA2, the penetrance is less than 20%. 6,7 Disease-associated alleles in BRCA1 and BRCA2 are uncommon in the U.S. population. It is estimated that between 0.01% and 0.1% of people carry mutations in BRCA1 that cause familial breast or ovarian cancer. 10 Similar carrier frequencies are estimated for BRCA2. Certain ethnic and regionally confined populations display a higher frequency of disease-producing alleles, among them Jewish people of Eastern European descent (Ashkenazi Jewish), who carry a limited number of mutations in both genes, which are present at much higher frequency than in the general population. Between 2.0% and 2.5% of Ashkenazi Jewish women carry one of three common mutations in the BRCA1 and BRCA2 genes. 11,12 For women in this group, hereditary breast cancer is a relatively common syndrome. Founding mutations are also present in other regional or ethnic populations, such as African Americans. 13 Reports about the distribution of BRCA1 and BRCA2 mutations and the characteristics of carriers frequently come from special groups, such as the Ashkenazim. Groups with a high frequency of restricted mutations are important for genetic analysis of penetrance, gene-gene interactions, gene-environment interactions, and the interaction with treatment and outcome. However, other studies benefit from less-biased populations. For instance, the spectrum of BRCA1 and BRCA2 mutations frequently come from high-risk clinics in large urban locations, which may not reflect mutations seen in more geographically dispersed populations. Clinical trials, patterns of care studies, and observations about medical decision-making are benefited by access to large and heterogeneous populations. The current study is from Duke University Medical Center, located in North Carolina and serving populations from rural and moderate-sized communities in the southeastern United States. In this study, we present the spectrum of mutations seen in BRCA1 and BRCA2 in our region of the country and present preliminary observations about the reaction of women after receiving genetic testing results.