Evaluation of Cardiotoxicity in HER-2-Positive Breast Cancer Patients Treated With Radiation Therapy and Trastuzumab

Abstract

Purpose: Trastuzumab is associated with cardiac dysfunction in patients with human epidermal growth factor receptor 2 (HER-2)–positive breast cancer. The current study examines the effect of radiation therapy (RT) on cardiotoxicity in this patient population. Methods and Materials: The Herceptin Adjuvant (HERA) trial is a phase 3 prospective, randomized clinical trial that established the efficacy of trastuzumab in HER-2–positive breast cancer. The current study is a retrospective analysis of 3321 trial patients treated with trastuzumab, with or without RT. Cardiac function was closely monitored over a median follow-up period of 11 years. The primary endpoint of the current study was to determine the effect of RT on left ventricular ejection fraction (LVEF) and the occurrence of cardiovascular events. Results: Patients were divided into 3 groups: 1270 patients received trastuzumab and left-sided RT (group 1); 1271 patients received trastuzumab and right-sided RT (group 2); and 780 patients received trastuzumab with no RT (group 3). The incidence of decline in LVEF documented by echocardiography was 9.18%, 8.99%, and 8.80%, respectively, with no significant differences among the 3 groups (P = .073). The incidence of cardiovascular events was low in all groups, with the lowest incidence noted in group 3 (0.62%) followed by group 2 (0.92%) and group 1 (1.08%) (P = .619). Univariate and multivariate competing-risks regression showed that left-sided and right-sided RT delivery did not significantly increase the risk of LVEF decline or cardiovascular events. Conclusions: Our analysis of the HERA trial suggests that RT does not significantly increase the risk of cardiotoxicity in HER-2–positive breast cancer patients treated with trastuzumab. Continued monitoring of patients is needed to investigate late effects of contemporary treatments for breast cancer patients. © 2022 Elsevier Inc.