BRCA1 MUTATIONS IN WOMEN ATTENDING CLINICS THAT EVALUATE THE RISK OF BREAST-CANCER

Background To define the incidence of BRCA1 mutations among patients s een in clinics that evaluate the risk of breast cancer, we analyzed DN A samples from women seen in this setting and constructed probability tables to provide estimates of the likelihood of finding a BRCA1 mutat ion in individual families. Methods Clinical information, family histo ries, and blood for DNA analysis were obtained from 263 women with bre ast cancer. Conformation-sensitive gel electrophoresis and DNA sequenc ing were used to identify BRCA1 mutations. Results BRCA1 mutations wer e identified in 16 percent of women with a family history of breast ca ncer. Only 7 percent of women from families with a history of breast c ancer but not ovarian cancer had BRCA1 mutations. The rates were highe r among women from families with a history of both breast and ovarian cancer. Among family members, an average age of less than 55 years at the diagnosis of breast cancer, the presence of ovarian cancer, the pr esence of breast and ovarian cancer in the same woman, and Ashkenazi J ewish ancestry were all associated with an increased risk of detecting a BRCA1 mutation. No association was found between the presence of bi lateral breast cancer or the number of breast cancers in a family and the detection of a BRCA1 mutation, or between the position of the muta tion in the BRCA1 gene and the presence of ovarian an cancer in a fami ly. Conclusions Among women with breast cancer and a family history of the disease, the percentage with BRCA1 coding-region mutations is les s than the 45 percent predicted by genetic-linkage analysis. These res ults suggest that even in a referral clinic specializing in screening women from high-risk families, the majority of tests for BRCA1 mutatio ns will be negative and therefore uninformative. (C) 1997, Massachuset ts Medical Society.