Efficacy of bilateral prophylactic mastectomy in BRCA1 and BRCA2 gene mutation carriers

Background: In women with a family history of breast cancer, bilateral prop hylactic mastectomy is associated with a decreased risk of subsequent breas t cancer of approximately 90%. We examined the association between bilatera l prophylactic mastectomy and breast cancer risk in women at high risk for breast cancer who also had mutations in BRCA1 and BRCA2 genes. Methods: We obtained blood samples from 176 of the 214 high-risk women who participated in our previous retrospective cohort study of bilateral prophylactic maste ctomy. We used conformation-sensitive gel electrophoresis and direct sequen ce analysis of the blood specimens to identify women with mutations in BRCA 1 and BRCA2. The carriers' probabilities of developing breast cancer were e stimated from two different penetrance models. Results: We identified 26 wo men with an alteration in BRCA1 or BRCA2. Eighteen of the mutations were co nsidered to be deleterious and eight to be of uncertain clinical significan ce. None of the 26 women has developed breast cancer after a median of 13.4 years of followup (range, 5.8-28.5 years). Three of the 214 women are know n to have developed a breast cancer after prophylactic mastectomy. For two of these women, BRCA1 and BRCA2 screening was negative, and no blood specim en was available for the third. Estimations of the effectiveness of prophyl actic mastectomy were performed, considering this woman as both a mutation carrier and a noncarrier. These calculationspredicted that six to nine brea st cancers should have developed among the mutation carriers, which transla tes into a risk reduction, after bilateral prophylactic mastectomy, of 89.5 %-100 % (95 % confidence interval = 41.4 % to 100%). Conclusions: Prophyla ctic mastectomy is associated with a substantial reduction in the incidence of subsequent breast cancer not only in women identified as being at high risk on the basis of a family history of breast cancer but also in known BR CA1 or BRCA2 mutation carriers.