Bilateral prophylactic mastectomy in BRCA mutation carriers: what surgeons need to know

Aim of this paper is to allows to analyze a topic of great relevance and media interest such as the role of prophylactic mastectomy in healthy women with BRCA mutation proposing to the surgeons some useful informations for decision-making. Less than 15% of all breast cancers are associated with germline genetic mutations. The majority of hereditary breast tumors are due to mutations in BRCA1 and BRCA2 genes that are responsible for only one third of hereditary cases. The risk estimates are extremely heterogeneous with a mean cumulative lifetime breast cancer risk of approximately 72% in BRCA1 and 69% in BRCA2 by age 80. The breast cancer is often bilateral and multicentric in BRCA mutation carriers. BRCA1 carriers have earlier-onset disease, particularly before age 50 and are more likely to develop aggressive triple-negative breast cancer than BRCA2 carriers or those who are BRCA mutation negative 1. Multiple strategies are effective in managing the risk of breast cancer in these women, including surveillance, chemoprevention, bilateral salpingo-oophorectomy and risk-reducing mastectomy. More intensive surveillance, including annual mammography and breast magnetic resonance imaging screening (commonly alternated every six months) beginning at age 25 or individualized based upon the earliest age of onset in the family, have significantly improved early detection of breast cancer among patients with deleterious BRCA mutations 1. The risk-reducing benefit of chemoprevention is not as well defined; chemopreventive strategies to reduce the risk of breast cancer have focused exclusively on prevention in high-risk women and involve the use of selective estrogen receptor modulators (SERMs) and aromatase inhibitors for breast cancer prevention. Only limited data are available regarding the preventive benefit of tamoxifene in BRCA mutations carriers 1. Risk-reducing bilateral salpingo-oophorectomy is recommended for BRCA mutation carriers by 35 to 40 or when childbearing is completed, or individualized based on age of onset of ovarian cancer in the family; bilateral salpingo-oophorectomy decreases the risk of both breast cancer and ovarian cancer in BRCA1 and BRCA2 mutation carriers and has also been associated with reduced all cause, breast cancer-specific, and ovarian cancer- specific mortality; risk-reducing bilateral salpingooophorectomy seems to offer an approximate 50% relative reduction in breast cancer risk 1. Prophylactic mastectomy provides the greatest reduction in risk of breast cancer development. In both retrospective and prospective observational studies, bilateral prophylactic mastectomy decreases the incidence of breast cancer by 90 percent or more in patients with BRCA mutation; it also is able to determine a variable gain in life expectancy compared to radiological surveillance; besides risk-reducing mastectomy allows to contain the strong anxiety and the fear of getting sick that often compromise the quality of life of BRCA mutation carriers 2. Prophylactic mastectomy could be technically performed in different ways. However, regarding the surgical technique, on the basis of current evidence, the gold standard seems to be represented by nipple-sparing mastectomy which, thanks to the preservation of the skin envelope and the nipple-areola complex, is able to optimize the oncological and aesthetic results. Nipple-sparing mastectomy provides superior cosmetic results. This procedure is usually performed through an inframmamary or radial or axillary incision where the skin is carefully dissected off the breast until all anatomic boundaries of the breast are reached and the gland in its entirety is excised. This technique does not seem to compromise the oncological/preventive efficacy compared to other types of mastectomy. In a multi-institution review of prophylactic 346 BRCA carriers undergoing either bilateral mastectomy or contralateral mastectomy with nipple- areola sparing there were no cases of breast cancer, where