Risk-reducing surgery for BRCA carriers (bilateral and contralateral mastectomy, salpingo-oophorectomy)

In the PROSE study, breast cancer was diagnosed in 2 of 105 BRCA1/2 carriers (1.9 percent) who had bilateral prophylactic mastectomy against 184 of 378 matched carriers (48.7 percent) who did not, over a mean 6.4 years, a risk reduction of about 90 percent with intact ovaries and 95 percent with prior or concurrent oophorectomy (Rebbeck 2004). A meta-analysis of 15 studies found bilateral prophylactic mastectomy reduced breast cancer risk in carriers (relative risk 0.114), contralateral prophylactic mastectomy reduced contralateral breast cancer (0.072) and all-cause mortality in carriers with breast cancer (hazard ratio 0.512), and prophylactic salpingo-oophorectomy reduced breast cancer risk (0.552) and all-cause mortality with and without breast cancer; bilateral mastectomy was not significantly associated with lower all-cause mortality (Li 2016). The oophorectomy effect on breast cancer is disputed: in a prospective cohort of 3,722 carriers with no cancer history, oophorectomy was not associated with breast cancer risk in BRCA1 carriers (hazard ratio 0.96) and protected BRCA2 carriers only before 50 (0.18) (Kotsopoulos 2017). NICE CG164 restricts bilateral risk-reducing mastectomy to a small proportion of women from high-risk families managed by a multidisciplinary team, with genetic counselling in a specialist clinic, verification of the family history where no mutation is identified, pre-operative counselling on psychosocial and sexual consequences and the possibility of finding a cancer in the specimen, discussion of immediate and delayed reconstruction with an oncoplastic team, access to support groups, no surveillance afterwards and no chemoprevention after the operation; the same restrictions apply to risk-reducing oophorectomy, and the combined pill should not be prescribed purely for ovarian risk reduction in a BRCA1 carrier considering oophorectomy before 40. Cancer Research UK explains that the surgeon cannot remove every breast cell, so the risk falls but does not vanish, and that reconstruction can be done at the same time or later. For carriers who already have triple-negative disease, the POSH authors advise weighing the prognosis of the first cancer before further surgery (Copson 2018).