Abstract
Childhood cancer survivors, particularly those who received chest radiotherapy, are at high risk for developing subsequent breast cancer. Minimizing long-term toxicity risks associated with additional radiotherapy and chemotherapy is a priority, but therapeutic tradeoffs have not been comprehensively characterized and their impact on survival is unknown. In this study, 431 female childhood cancer survivors with subsequent breast cancer from a multicenter retrospective cohort study were evaluated. Compared with one-to-one matched females with first primary breast cancer, survivors are as likely to be prescribed guideline-concordant treatment (N = 344 pairs; survivors: 94%, controls: 93%), but more frequently undergo mastectomy (survivors: 81%, controls: 60%) and are less likely to be treated with anthracyclines (survivors: 47%, controls: 66%) or radiotherapy (survivors: 18%, controls: 61%). Despite this, survivors have nearly 3.5-fold (95% CI = 2.17-5.57) greater mortality risk. Here, we show survivors with subsequent breast cancer face excess mortality despite therapeutic tradeoffs and require specialized treatment guidelines.