Prophylactic mastectomy for BRCA mutation carriers after ovarian cancer treatment: is it beneficial?

Prophylactic mastectomy is now being offered to healthy women with a BRCA1 or BRCA2mutation in order to reduce the incidence and mortality of hereditary breast cancer, as well as to relieve cancer-related distress [1]. Since Angelina Jolie underwent prophylactic bilateral mastectomy in 2013, there has been an upsurge in the number of referrals for genetic testing and in the number of preventive surgeries performed [2,3]. Actual data on the effectiveness of preventive mastectomy show that it reduces cancer incidence, but it is yet to be seen if it reduces mortality as well [4]. Nevertheless, it is predicted from modeling of cancer rates that preventive breast surgery will favorably impact on life expectancy. Giannakeas and Narod conducted a series of simulations, using published age-specific cancer incidence and mortality rates, and estimated the lifetime probability of dying of breast cancer for women with a mutation who did and who did not have preventive mastectomies [5]. The expected benefit of preventive mastectomy on BRCA-associated breast cancer mortality varied dramatically based on the age at the surgery. Specifically, mastectomy at age 25 had the greatest impact on bettering life expectancy (3.3 years gained) but the benefit was much less if performed at age 55 (0.7 years gained). For women who underwent surgery after age 50, there was a substantial reduction in cancer risk but only a modest reduction in cancer mortality. What about the woman who has a personal history of ovarian cancer? Is there any benefit to doing a preventive mastectomy after a diagnosis of ovarian cancer? This is a valid question – the risk of developing breast cancer among women with a BRCA1 or BRCA2 mutation is 2% annually, and the risk from age 50 to 70 may exceed 40% [6]. Importantly, these women are also at risk of ovarian cancer recurrence and may not survive to see the benefit of preventive mastectomy take effect. Given the high case-fatality rate of ovarian cancer, the life expectancy of a patient with BRCA-associated ovarian cancer may be too short to warrant preventive surgery [7]. The actuarial survival at 10 years among patients with serous ovarian cancer is estimated at 34% for BRCA1 mutation carriers and 22% for BRCA2 mutation carriers [8]. In a follow-up study, we recently estimated both the risk of breast cancer after a diagnosis of ovarian cancer and the impact of preventive mastectomy on all-cause mortality [9]. Among 509 BRCA mutation carriers with a personal diagnosis of ovarian cancer, we reported that 20 women (3.9%) developed breast cancer, on average, 3.5 years since the ovarian cancer diagnosis. Given this information, we estimated that the 10-year actuarial risk of developing breast cancer, conditional on survival, to be 7.8%; however, this was substantially decreased to 3.9% when competing deaths from ovarian cancer and other deaths were included. Armed with these statistics, using a simulation approach, we evaluated the benefit of preventive mastectomy on all-cause mortality among women with ovarian cancer. Overall, there was little improvement in survival with preventive breast surgery (<2% reduction in overall mortality to age 80) for ovarian cancer patients. Yet, the impact of mastectomy on mortality was dependent on the age of the patients, the ovarian cancer stage, and the time elapsed since diagnosis. If a woman was diagnosed with ovarian cancer before age 50 and survived for 10 years without a recurrence, the reduction in all-cause mortality to age 80 was 3.3% – a small but significant gain but may be worth the trade-off. For patients with early-stage ovarian cancer, survival is generally good and recommending a prophylactic mastectomy is easier. This is important if a woman has ovarian cancer diagnosed at the time of preventive oophorectomy. For example, in the study by Finch et al., the 5-year overall survival among women with occult disease was 92% (compared to 54% for women with clinically detected ovarian cancer) and for them a preventive mastectomy might be warranted [10]. In a paper by Cortesi et al., the survival of women with screen-detected (i.e. ultrasound and CA-125 levels) ovarian cancers had a 75% 5-year survival, (but 10-year survival rates were not reported) [11]. Nevertheless, screening with ultrasound and CA-125 is not considered standard of care for high-risk women because the benefits have not been clarified. In conclusion, we recommend that preventive mastectomy be considered for ovarian cancer patients if they are diagnosed through preventive surgery or if they have stage I/II disease. For patients with stage III/IV disease, we recommend that preventive mastectomy be considered if they are 10 years from diagnosis, are age 55 or below, and if they have a serum CA125 level within normal limits.