Breast conservation therapy for invasive breast cancer in Ashkenazi women with BRCA gene founder mutations

Background: Germline mutations in the BRCA1 and BRCA2 genes are associated with an increased risk of breast cancer. Whether women with breast cancer w ho have inherited mutations in these genes have a different outcome after b reast conservation therapy than women with "sporadic" cancer is unresolved, Consequently,,ve compared the outcomes after breast conservation therapy i n Ashkenazi women with or without germline mutations in BRCA1 and/or BRCA2 (hereafter called BRCA), Methods: We studied 305 women of Ashkenazi Jewish descent undergoing breast-conserving treatment for 329 invasive breast canc ers, We reviewed their clinical records, retrieved their archival tissue sa mples, and tested those samples for the founder mutations BRCA1 185delAG, B RCA1 5382insC, and BRCA2 6174delT, Genetic results were linked to clinical data and outcomes by univariate and multivariate analyses. All P values are two-sided. Results: We detected mutations in BRCA genes in 28 of 305 women , Women with BRCA mutations were more likely to be diagnosed with cancer be fore the age of 50 years (P<.001) and to have lymph node involvement (P =.0 4). Ipsilateral breast tumor recurrence was more common in women with BRCA mutations, although this did not reach statistical significance (relative r isk [RR] = 1.79; 95% confidence interval [CI] = 0.64-5.03), Women with muta tions were more likely to develop contralateral breast cancer (RR = 3.50; 9 5% CI = 1.78-8.74; P =.001). Distant disease-free survival was shorter in w omen with mutations (66.2% versus 84.3% at 10 years; P =.05), as was breast cancer-specific survival (71.9% versus 87.2% at 10 years; P =.02). Tumor s tage and nodal status, but not mutation status, were predictive of distant disease-free and breast cancer-specific survival in multivariate analysis, Conclusions: Women with BRCA founder mutations are at increased risk for br east cancer-related events after breast conservation. However, mutation sta tus is not an independent predictor of survival and should not influence de cisions regarding adjuvant therapy. The increased contralateral breast canc er risk in women heterozygous for BRCA mutations mandates careful surveilla nce.