Age-specific ovarian cancer risks among women with a BRCA1 or BRCA2 mutation.

OBJECTIVES: For women at high risk of developing ovarian cancer, it is important to provide an accurate recommendation for the optimal age for preventive surgery in order to maximize the preventative effect while delaying symptoms associated with early surgical menopause. The goal of the current study was to estimate age-specific incidence rates of ovarian cancer among women with a BRCA1 or BRCA2 mutation.

METHODS: From our international registry, we identified 5689 women with no previous diagnosis of ovarian or fallopian tube cancer or preventive oophorectomy. Women were followed from the date of completion of the baseline questionnaire until either a diagnosis of ovarian or fallopian tube cancer, prophylactic oophorectomy, death or last follow-up. The annual and cumulative incidence rates of ovarian cancer were estimated.

RESULTS: Over a mean follow-up period of 4.7 years (ranges 0-22.6), 195 incident ovarian or fallopian tube cancers were diagnosed (169 [86%] ovarian cancers, 22 [11%] fallopian tube cancers and four [2%] cancers that involved both the ovaries and fallopian tubes). Of these, 45 (23%) cancers were diagnosed at preventive surgery (occult cancers). The cumulative risk of ovarian cancer to age 80 was 49% for BRCA1 and 21% for BRCA2 mutation carriers. The mean age at diagnosis was 51.3 years (ranges 33-84) among women with a BRCA1 mutation and 61.4 years (ranges 44-80) among women with a BRCA2 mutation.

CONCLUSION: Based on a cumulative risk of 0.55% to age 35 for BRCA1 mutation carriers and of 0.56% to age 45 for BRCA2 mutation carriers, we recommend bilateral salpingo-oophorectomy before age 40, but ideally by age 35, for women with a BRCA1 mutation and by age 45 for those with a BRCA2 mutation to maximize prevention and to minimize adverse effects.