Increased risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers after breast-conserving therapy compared to mastectomy

Abstract

1512 Background: BRCA mutation carriers affected by breast cancer face an elevated risk of contralateral breast cancer (clBrCa). We here aimed at estimating the influence of breast conserving therapy (BCT) versus mastectomy (MXT) on the rik of clBrCa. Methods: We conducted a retrospective cohort study in 3810 index patients (pts) collected within the CHBOC. Deleterious BRCA1 or BRCA2 mutations were detected in 921 pts and medical records were obtained from 532 pts (344 BRCA1, 184 BRCA2 mutation carriers, 4 both) of whom 261 (49%) underwent BCT and 271 (51%) MXT. Pts were followed from the initial diagnosis of breast cancer until clBrCa or censored at time of prophylactic contralateral mastectomy, oophorectomy, death, or date of last visit. Median age at first diagnosis was 39.9 years (range 17.5 to 79.0) and median follow up 48.84 months (3413 person years). The hazard ratio (HR) was estimated using multivariate Cox regression analysis adjusting for conduct of radiotherapy, age at first breast cancer, and affected BRCA gene. Results: In the univariate analysis the risk of clBrCa was 12.2% (95% CI 7.6 to 16.8) at 5 years and 24.9% (95% CI 18.0 to 31.9) at 10 years for pts treated with MXT and 25.9% (95% CI 18.8 to 33.1) at 5 years and 45.7% (95% CI 35.0 to 56.5) at 10 years for pts treated with BCT. In the multivariate analysis, the HR was 1.8 for BCT versus MXT (95% CI 1.2 to 2.7). Neither age at diagnosis of the first primary nor BRCA mutation status were significantly predictive. A subgroup analysis comparing BCT plus radiotherapy with MXT minus radiotherapy revealed a HR of 1.6 (95% CI 1.02 to 2.56) for the BCT group. Conclusions: We report for the first time a 1.8-fold increased risk of clBrCa in BRCA mutation carriers undergoing BCT versus MXT. Scattered radiation is the most probable causation. Although results from further studies such as the WECARE study should be awaited, our results provide evidence that recommendations for primary brCa treatment of BRCA mutation carriers must to be reconsidered. No significant financial relationships to disclose.