High risk for ovarian cancer in a prospective series is restricted to BRCA1/2 mutation carriers.

PURPOSE Inherited ovarian cancer carries a serious prognosis. Prophylactic oophorectomy has been advocated. The degree to which inherited ovarian cancer is restricted to BRCA mutation carriers is not fully known. We wanted to determine the prevalence of BRCA mutation carriers in women at high risk from ovarian cancer. EXPERIMENTAL DESIGN Healthy women who were found to be at increased risk judged by family history were followed prospectively. Full BRCA1/2 mutation analysis was conducted on all patients who contracted pelvic cancer. RESULTS We identified 1,582 women at risk during 5,674 person-years. Forty infiltrating epithelial ovarian cancers, six peritoneal cancers, and one fallopian tube cancer were diagnosed. All but one of these patients (98%) had a BRCA mutation, a frequency that was significantly higher than for the 3 patients with borderline ovarian cancers, who were all mutation negative (P = 0.0002). Eighty-two percent of the detected mutations belonged to one of the 10 Norwegian founder mutations previously reported. At prophylactic bilateral salpingo-oophorectomy, cancer was found in 18 of 345 (5.2%) of mutation carriers compared with none in the 446 mutation negative (P = 0.0000). CONCLUSIONS In healthy women with a family history of ovarian cancer, high risk for ovarian cancer was restricted to BRCA1/2 mutation carriers. A woman at risk for ovarian cancer according to her family history should have access to full BRCA1/2 mutation testing before deciding on prophylactic bilateral salpingo-oophorectomy.