Exercise-based cardio-oncology rehabilitation for cardiotoxicity prevention during breast cancer chemotherapy: the ONCORE randomized controlled trial

[Abstract] Background: Breast cancer (BC) treatment with anthracyclines and/or anti-human epidermal growth factor receptor-2 (HER2) antibodies is associated with an increased risk of cardiovascular disease complications, including cancer therapy-related cardiac dysfunction (CTRCD). While Cardio-Oncology Rehabilitation (CORe) programs including exercise have emerged to minimize these risks, its role in preventing CTRCD is unclear. Objectives: We investigated the effectiveness of an exercise-based CORe program in preventing CTRCD [left ventricular ejection fraction (LVEF) drop ≥10% to a value 15% in global longitudinal strain (GLS)]. Secondary outcomes examined changes in cardiac biomarkers, physical performance including peak oxygen consumption, psychometric and lifestyle outcomes. Safety, adherence, and patient satisfaction were also assessed. Methods: This is a randomized controlled trial including 122 early-stage BC women receiving anthracyclines and/or anti-HER2 antibodies, randomized to CORe (n = 60) or usual care with exercise recommendation (n = 62). Comprehensive assessments were performed at baseline and after cardiotoxic treatment completion. The average duration of the intervention was 5.8 months. Results: No cases of CTRCD were identified during the study. LVEF decreased in both groups, but was significantly attenuated in the CORe group [-1.5% (-2.9, -0.1); p = 0.006], with no changes detected in GLS or cardiac biomarkers. The CORe intervention led to significant body mass index (BMI) reduction (p = 0.037), especially in obese patients [3.1 kg/m2 (1.3, 4.8)]. Physical performance and quality-of-life remained stable, while physical activity level increased in both groups. No adverse events were detected. Conclusions: This study suggests that CORe programs are safe and may help attenuate LVEF decline in BC women receiving cardiotoxic therapy and reduce BMI in obese patients.This work was supported by a competitive grant from the Spanish Association Against Cancer Scientific Foundation (grant number PRDLC21480DÍAZ) and a competitive grant from the Spanish Health Research Fund of the Carlos III Health Institute (grant number PI17/01687), co-funded by FEDER, through Strategic Action in Healthcare, 2017. Funding for open access charge will be supported by Universidade da Coruña/CISUG. None of the funding sources were involved in the study design, data collection, data analysis, data interpretation or report writing.Asociación Española contra el Cáncer; PRDLC21480DÍAZinfo:eu-repo/grantAgreement/ISCIII/Programa Estatal de Fomento de la Investigación Científica y Técnica de Excelencia/PI17%2F01687/PROGRAMAS INTEGRADOS DE REHABILITACION CARDIACA CON EJERCICIO FISICO EN LA PREVENCION DE LA TOXICIDAD CARDIOVASCULAR MEDIADA POR ANTRACICLINAS Y/O ANTICUERPOS ANTI-HER-2. ESTUDIO ONCOR