Total body irradiation (TBI) and risk of breast subsequent malignant neoplasm (SMN) after blood or marrow transplantation (BMT): A report from the BMT survivor study (BMTSS).

Abstract

11572 Background: The association between TBI and breast SMN in BMT recipients is not clearly defined. We address this limitation to develop evidence for screening guidelines for those at risk. Methods: Study participants were drawn from BMTSS – a multi-site retrospective cohort of patients who had received BMT between 1974 and 2014 and survived ≥2y post-BMT. Participants completed the BMTSS survey that included sociodemographics and health conditions. Breast SMN was confirmed by pathology report review. Clinical characteristics, pre-BMT and BMT exposures were abstracted from medical records. Using multivariable Cox proportional hazards models, freedom from breast SMN was measured from birth and TBI was treated as a time-varying covariate in analyses stratified by type of BMT (allogeneic; autologous). Results: 1546 female participants (allogeneic 808; autologous 738) received BMT at a mean age of 43.1±17.6y and were followed for 9.4±7.7y; primary diagnoses: HL/NHL (28%), AML/MDS (27%), PCD (19%), other (28%). TBI was used in 671 patients (allogeneic 57%; autologous 30%). Patients with pre-BMT chest radiation (n = 45) were excluded from the analysis. A total of 38 cases of breast SMN were identified (allogeneic 19; autologous 19). Allogeneic BMT: exposure to TBI (HR = 3.4; 95%CI 1.1-10.9, p = 0.04) and age at BMT < 40y (HR = 4.0; 95%CI 1.3-12.8, p = 0.02) were associated with increased risk of breast SMN. Risk of breast SMN was higher and breast SMN developed earlier among those exposed to TBI before age 40y vs. those exposed after 40y (8.7% vs. 0% by attained age 50; 10.6% vs. 5.8% by attained age 60, p = 0.003). Autologous BMT: Age < 40y was associated with a 4.8-fold higher risk (95%CI 1.1-20.1, p = 0.03) of breast SMN. TBI was associated with a 2-fold higher risk (p = 0.2). The cumulative incidence of breast SMN among those exposed to TBI at age < 40y vs. age ≥40y was 5.1% vs. 2.4% by attained age 60 (p = 0.07). Conclusions: TBI is associated with breast SMN among allogeneic BMT recipients. The risk is especially high and occurs at a younger age, among those exposed at age < 40y. These findings provide evidence for initiating screening at a young age after exposure to TBI.