Radiation Associated Secondary Malignancies in BRCA Mutation Carriers Treated for Breast Cancer

Abstract Background Radiation therapy (RT), a standard Breast Cancer (BC) treatment modality, is associated with a small increased risk of in-field second primary malignancy (SPM). SPM rates following RT in BRCA mutation carriers, have rarely been reported. An elevated risk of SPM would impact the safety of breast conservation for early BC or prophylactic radiation as a method of prevention. We analyzed a population of BRCA carriers irradiated for BC to determine if there is an elevated rate of SPM. Methods BC patients treated with breast/chestwall RT +/- regional lymph nodes between 1991-2012 at a single institution who were BRCA 1/2 carriers were retrospectively identified. Only those with > 5 years of follow up with adequate demographic, tumor, and radiation data were included. SPMs were recorded and previously delivered RT doses to the organ/site of malignancy were determined. Results 230 women, of whom 80% carried an Ashkenazi Jewish founder mutation, met entry criteria with 3D-RT delivered to 266 breasts/chest walls including regional nodes in 110 (41%). With a median follow-up of 10 years (range 5-27, mean 11.4) comprising 3,042 person-years, six SPMs developed of which only one (papillary thyroid carcinoma) was within the radiation field (crude rate of 0.38% of irradiated breasts/chestwalls), diagnosed 17 years after RT. This corresponds to an incidence of 0.32/1000 woman-years. The Kaplan-Meier estimate of 20-year freedom from a radiation-induced SPM is 99.5%. Calculated dose exposure to the out-of-field SPMs ranged from 0.1-1Gy. No patient developed an in-field skin cancer or sarcoma. Conclusion In this largest cohort of women treated with radiotherapy for BRCA-associated breast cancer, we identified no signal for an increased risk of radiation-induced SPMs compared to the general BC population, and the risk is extraordinarily small. While larger cohorts and longer follow-up are needed, these results support the safety of RT in BRCA carriers.