Elevated Risk of Radiation Therapy-Associated Second Malignant Neoplasms in Young African-American Women Survivors of Stage I-IIIA Breast Cancer.

Abstract

To estimate the effect of radiation therapy (RT) on nonbreast second malignant neoplasms (SMNs) in young women survivors of stage I-IIIA breast cancer. Women aged 20 to 44 years who received a diagnosis of stage I-IIIA breast cancer (1988-2008) were identified in the Surveillance, Epidemiology, and End Results 9 registries. Bootstrapping approach and competing-risk proportional hazards models were used to evaluate the effect of RT on nonbreast SMN risk. The analysis was repeated in racial subgroups. Radiotolerance score analysis of normal airway epithelium was performed using Gene Expression Omnibus (GEO) data sets. Within records of 30,003 women with primary breast cancer, 20,516 eligible patients were identified, including 2,183 African Americans (AAs) and 16,009 Caucasians. The 25-year cumulative incidences of SMN were 5.2% and 3.6% (RT vs no-RT) for AAs, with 12.8-year and 17.4-year (RT vs no-RT) median follow-up (hazard ratio [HR] = 1.81; 95% bootstrapping confidence interval [BCI], 1.02-2.50; P < .05), respectively, and 6.4% and 5.9% (RT vs no-RT) for Caucasians with 14.3-year and 18.1-year (RT vs no-RT) median follow-up (HR = 1.10; 95% BCI, 0.61-1.40; P > .05), respectively. The largest portion of excess RT-related SMN risk was lung cancer (AA: HR = 2.08, 95% BCI, 1.02-5.39, P < .05; Caucasian: HR = 1.50, 95% BCI, 0.84-5.38, P > .05). Subpopulation Treatment Effect Pattern Plot (STEPP) analysis revealed higher post-RT nonbreast SMN risk in those 20 to 44 years of age, with larger HRs for RT in AAs. Radiotolerance score (RTS) of normal airway epithelium from young AA women was significantly lower than that from young Caucasian women (P = .038). With a projected 25-year follow-up, RT is associated with elevated risk of nonbreast SMNs, particularly second lung cancer, in young women survivors of stage I-IIIA breast cancer. Nonbreast SMNs associated with RT are higher in AA women than Caucasian women.