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.