Clinical outcome for BRCA1 and BRCA2 mutation carriers after contralateral prophylactic mastectomy

Studies have shown that (bilateral) prophylactic mastectomy in genetically predisposed populations reduces the risk of breast cancer. Since BRCA1 and BRCA2 germline mutation testing became widely available (1995), breast cancer patients with a family history of breast cancer have also been tested. After having been identified as a BRCA1 or BRCA2 carrier, some women decide to undergo a contralateral prophylactic mastectomy (CPM) while others choose for intensive surveillance. The impact of this choice on contralateral breast cancer incidence and survival is still unknown.

We identified a cohort of 148 female BRCA1 or BRCA2 mutation carriers (115 and 33, respectively) who previously were treated for unilateral invasive breast cancer stage I–IIIa. Seventy-nine women underwent a CPM, while the other women remained under intensive surveillance. The mean follow-up was 3.5 years and started at the time of CPM or at the date of mutation testing, whichever came last (i.e. on average, 5 years after diagnosis of the first breast cancer).

One woman developed an invasive contralateral primary breast cancer after CPM, whereas six were observed in the surveillance group (P < 0.001). CPM reduced the risk of contralateral breast cancer by 91%, independent of the effect of bilateral prophylactic oophorectomy (BPO). At 5-year follow-up, overall survival was 94% for the CPM group versus 77% for the surveillance group (P = 0.03). Unexpectedly, this difference in survival was mostly due to higher mortality related with the first breast cancer and ovarian cancer in the surveillance group. After adjustment for BPO in a multivariate Cox analysis, the CPM effect on overall survival was no longer significant.

Our data show that CPM markedly reduces the risk of contralateral breast cancer among BRCA1 or BRCA2 mutation carriers with a history of breast cancer. Longer follow-up is needed to study the impact of CPM on contralateral breast cancer specific survival. The choice for CPM is highly correlated with that for BPO while only BPO so far leads to a significant improvement in overall survival.