Prospective cohort study of projected benefit of bilateral salpingo-oophorectomy by age in BRCA carriers

Women with a BRCA1 or BRCA2 variant face a high lifetime risk ovarian cancer and are often advised to undergo preventive surgery (bilateral salpingo-oophorectomy; BSO) before cancer develops. The recommended age of BSO is 35 years for BRCA1 carriers and 45 years for BRCA2 carriers, but some women choose to delay surgery until menopause; there is no standard upper age at which surgery is no longer advised. A prospective cohort study in a multinational cohort of BRCA carriers was carried out to estimate the residual lifetim risk of ovarian cancer by current age and projected age at BSO. A total of 4286 BRCA1 and 1427 BRCA2 carriers between the ages of 30 and 74 years at baseline (mean age 42.0 years, SD 10.8) were recruited across 24 centers. The mean follow-up was 4.4 years (SD 3.9). There were 249 incident ovarian cancers in the follow-up period. The lifetime risk of ovarian cancer was 55.0% (95% CI 48.8-61.9) for a BRCA1 carrier and 24.1% (15.1-36.6) for a BRCA2 carrier. A 30-year old BRCA1 carrier with BSO delayed to age 50 years had a projected residual ovarian cancer risk of 23.9% (95% CI 20.7-27.4). At age 75 years, the residual risk of ovarian cancer was estimated to be 8.4% (95% CI 1.7-22.7) for a BRCA1 carrier and 3.7% (0.1-22.7) for a BRCA2 carrier. The authors conclude that the residual risk of ovarian cancer for older women in good health is sufficiently high to consider preventive surgery. BRCA1 carriers who defer BSO until age 50 years may face a subtantial risk of developing ovarian cancer.