SEQUENCE-ANALYSIS OF BRCA1 AND BRCA2 - CORRELATION OF MUTATIONS WITH FAMILY HISTORY AND OVARIAN-CANCER RISK

Purpose: Previous studies of mutations in BRCA1 or BRCA2 have used det ection methods that may underestimate the actual frequency of mutation s and have analyzed women using heterogeneous criteria for risk of her editary cancer. Patients and Methods: A total of 238 women with breast cancer before age 50 or ovarian cancer at any age and at least one fi rst- or second-degree relative with either diagnosis underwent sequenc e analysis of BRCA1 followed by analysis of BRCA2 (except for 27 women who declined analysis of BRCA2 after a deleterious mutation was disco vered in BRCAI). Results were correlated with personal and family hist ory of malignancy. Results: Deleterious mutations were identified in 9 4 (39%) women, including 59 of 117 (50%) from families with ovarian ca ncer and 35 of 121 (29%) from families without ovarian cancer. Mutatio ns were identified in 14 of 70 (20%) women with just one other relativ e who developed breast cancer before age 50. In women with breast canc er, mutations in BRCAI and BRCA2 were associated with a 10-fold increa sed risk of subsequent ovarian carcinoma (P = .005). Conclusion: Becau se mutations in BRCA1 and BRCA2 in women with breast cancer are associ ated with an increased risk of ovarian cancer, analysis of these genes should be considered for women diagnosed with breast cancer who have a high probability of carrying a mutation according to the statistical model developed with these data. (C) 1998 by American Society of Clin ical Oncology.