Development of Cancer Therapy-Related Cardiac Dysfunction Is Associated With Disease Progression in Breast Cancer

Background: Cancer therapy-related cardiac dysfunction (CTRCD) is a recognized complication of breast cancer treatment. Although early detection using cardiac biomarkers such as cardiac troponin I (cTnI) is recommended, the impact of CTRCD on cancer prognosis remains unclear. Methods and Results: We conducted a prospective observational study of 273 patients with breast cancer treated with anthracycline-based chemotherapy and/or human epidermal growth factor receptor 2 (HER2)-targeted therapy at Fukushima Medical University between January 2016 and July 2022. Serial measurements of cTnI, B-type natriuretic peptide (BNP), and echocardiographic parameters were performed at baseline and at 3, 6, 12, and 24 months. CTRCD was defined based on declines in left ventricular ejection fraction (LVEF) and categorized as mild, moderate, or severe. CTRCD occurred in 40 (14.7%) patients. Even mild CTRCD was associated with greater reductions in LVEF at 12 months in patients with elevated cTnI, although recovery was observed by 24 months. Kaplan-Meier analysis revealed significantly shorter progression-free survival in the CTRCD group. In multivariable analysis, CTRCD was an independent predictor of cancer progression (hazard ratio 2.50; 95% confidence interval 1.17-5.36; P=0.018). Conclusions: CTRCD following cardiotoxic chemotherapy was associated with reduced progression-free survival in patients with breast cancer. These findings underscore the importance of early CTRCD detection not only for cardiac protection but also as a prognostic indicator in cancer management.