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

PURPOSE/OBJECTIVE(S): Trastuzumab is associated with cardiac dysfunction in HER-2 positive breast cancer patients. The current study examines the effect of radiation therapy on cardiotoxicity in this patient population. MATERIALS/METHODS: The HERA trial is a phase III prospective randomized clinical trial that established the efficacy of trastuzumab in HER-2 positive breast cancer. The current study is a retrospective analysis of 3,321 trial patients treated with trastuzumab with or without radiotherapy. Cardiac function was closely monitored over a median follow up period of 10 years. The primary endpoint of the study was to determine the effect of radiation therapy on left ventricular ejection fraction (LVEF) and the occurrence of cardiovascular events. RESULTS: Patients were divided to three groups: 1270 subjects received trastuzumab and left-sided radiation therapy (group 1), 1271 subjects received trastuzumab and right-sided radiation therapy (group 2) and 780 had trastuzumab with no radiation therapy (group 3). The incidence of significant LVEF decline was 28.22%, 29.54% and 26.85%, respectively with no significant differences among the three groups (P-value = 0.484). 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-value = 0.619). Univariate and multivariate COX regression showed significant associations of age and hypertension with both LVEF decline and cardiovascular events. However, radiation therapy delivery and laterality were not significantly associated with either outcome. CONCLUSION: Our analysis of the HERA trial suggests that radiation therapy 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.SCOPUS: ar.jDecretOANoAutActif