Ovarian cancer after breast cancer in women with a BRCA1 or BRCA2 pathogenic variant

OBJECTIVE: Inherited BRCA1/2 pathogenic variants (mutations) confer high lifetime risks of breast and ovarian cancers. Estimating the cumulative ovarian cancer risk following a breast cancer diagnosis in these women will help guide decisions regarding preventive salpingo-oophorectomy. METHODS: Women carrying a BRCA1 or BRCA2 mutation were followed after breast cancer and completed follow-up questionnaires every two years. The 15-year cumulative risk of ovarian cancer was estimated for women with a prior history of breast cancer and for matched control women without breast cancer. RESULTS: A total of 2084 BRCA carriers with breast cancer (1515 BRCA1, 569 BRCA2) were included. During a mean follow-up of 3.9 years, 71 ovarian/fallopian carcinomas were diagnosed (66 BRCA1, 5 BRCA2). The 15-year cumulative ovarian cancer risk was 14.9 % in BRCA1 and 5.1 % in BRCA2 carriers. Women with breast cancer were compared to those without; 1378 matched pairs were included. The 15-year cumulative risk of ovarian/fallopian cancer was 10.8 % in women with a history of breast cancer versus 25.9 % in those without. Among BRCA1 carriers, the risk was 12.2 % in women with breast cancer and 32.0 % in those without. Among BRCA2 carriers, the 15-year ovarian cancer risk was 2.0 % in both groups. CONCLUSIONS: Ovarian cancer risk remains high in BRCA1/2 carriers following breast cancer diagnosis. For BRCA1 mutation carriers, the risk is lower than in women without breast cancer. However, for both BRCA1 and BRCA2 the ovarian cancer risk is elevated, and considering the poor prognosis associated with ovarian cancer, risk-reducing salpingo-oophorectomy is strongly recommended for women with BRCA-associated breast cancer.