Exercise to Prevent Anthracycline-Induced Cardiotoxicity (EXACT2.0) in Females with Breast Cancer

Abstract

The cardioprotective effects of aerobic exercise (AE) in mitigating anthracycline (AC)-induced cardiotoxicity in females with breast cancer (BC) remain unclear. This study investigated the impact of a 24-week home-based AE program on cardiac function, VO2peak, fatigue, and health-related quality of life (HRQoL) in females with BC receiving AC. Participants (N=20; 52±10 years-old) were randomized to standard of care (SOC; n=10) or SOC+24-week home based AE program (AEX; n=10). The exercise program consisted of two self-directed sessions per week (35-85% incremental heart rate reserve) to achieve 90-minutes of exercise weekly. Cardiac function [left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS)], were assessed using serial transthoracic echocardiography at baseline and at 24-weeks. Total time exercising during the Bruce treadmill exercise stress test performed at baseline and 24-week follow-up was used to calculate VO2peak. At baseline, mean LVEF was 62.2±1.4% and 63.1±1.6% in the SOC and AEX group, respectively (p=0.247; r=-0.27). After 24-weeks, mean LVEF was 61.9±2.7% and 58.9±7.3% in the SOC and AEX groups, respectively (p=0.905; r=0.04). At baseline, the GLS was -18.9±1.6% and -19.1±1.2% in the SOC and AEX groups, respectively. After 24-weeks, the GLS was -18.3±1.2% and -17.3±2.2% in the SOC and AEX groups, respectively. There was no significant Group × Time interaction effect for GLS (p=0.241; p 2=0.080). At baseline, the mean VO2peak was 23.4±3.29 mL/kg/min and 28.9±9.23 mL/kg/min in the SOC and AEX groups, respectively (p=0.232; r=-0.33). At 24- weeks, mean VO2peak was 23.3±8.2 mL/kg/min and 32.2±7.8mL/kg/min in the SOC and AEX groups, respectively (p=0.049). At baseline, the mean HRQoL was 104.3±16.5 and 110.8±6.9 in the SOC and AEX groups, respectively. At 24- weeks, mean HRQoL was 109.6±14.4 and 112.1±11.2 in the SOC and AEX groups, respectively. There was no significant Group × Time interaction effect for HRQoL (p=0.351; p 2 =0.051). At baseline, the mean fatigue was 39.8±8.3 and 41.1±5.4 in the SOC and AEX groups, respectively. At 24- weeks, mean fatigue was 34.2±9.2 and 33±12.4 in the SOC and AEX groups, respectively. There was no significant Group × Time interaction effect at follow-up compared to baseline for fatigue (p=0.651; p 2 =0.012). The findings of this study demonstrated that the 24-week aerobic exercise program deployed by EXACT2.0 was insufficient at mitigating decreases in indices of cardiotoxicity (i.e., LVEF, GLS), VO2peak, and patient reported levels of HRQoL and fatigue. It is possible that shortcomings in patient recruitment (e.g., underpowered), exercise prescription, and protocol design, each ultimately limited due to a global pandemic, contributed to the results reported herein.