Breast cancer after prophylactic bilateral mastectomy in women with a BRCA1 or BRCA2 mutation.

Background: Women with a BRCA1 or BRCA2 mutation have a high risk of breast cancer and may choose to undergo prophylactic bilateral total mastectomy. We investigated the efficacy of this procedure in such women. Methods: We conducted a prospective study of 139 women with a pathogenic BR CA1 or BRCA2 mutation who were enrolled in a breast-cancer surveillance pro gram at the Rotterdam Family Cancer Clinic. At the time of enrollment, none of the women had a history of breast cancer. Seventy-six of these women ev entually underwent prophylactic mastectomy, and the other 63 remained under regular surveillance. The effect of mastectomy on the incidence of breast cancer was analyzed by the Cox proportional-hazards method in which mastect omy was modeled as a time-dependent covariate. Results: No cases of breast cancer were observed after prophylactic mastect omy after a mean (+/-SE) follow-up of 2.9+/-1.4 years, whereas eight breast cancers developed in women under regular surveillance after a mean follow- up of 3.0+/-1.5 years (P=0.003; hazard ratio, 0; 95 percent confidence inte rval, 0 to 0.36). The actuarial mean five-year incidence of breast cancer a mong all women in the surveillance group was 17+/-7 percent. On the basis o f an exponential model, the yearly incidence of breast cancer in this group was 2.5 percent. The observed number of breast cancers in the surveillance group was consistent with the expected number (ratio of observed to expect ed cases, 1.2; 95 percent confidence interval, 0.4 to 3.7; P=0.80). Conclusions: In women with a BRCA1 or BRCA2 mutation, prophylactic bilatera l total mastectomy reduces the incidence of breast cancer at three years of follow-up. (N Engl J Med 2001;345:159-64.) Copyright (C) 2001 Massachusett s Medical Society.