Exercise to prevent anthracycline-based cardio-toxicity (EXACT 2.0) in women with breast cancer
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Date
2021-06
Authors
Varghese, Sonu
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Abstract
Background: Cardiotoxicity from breast cancer (BC) therapy, specifically anthracyclines, is a significant cause of morbidity and mortality in women with BC. Although aerobic exercise (AE) during anthracycline therapy has been shown to reduce side effects including fatigue, nausea, and pain, the cardioprotective benefits of exercise remain unclear. We investigated the effect of a 24-week home-based AE program on cardiac function in women with BC receiving anthracyclines using echocardiography, treadmill testing, and quality of life surveys.
Methods: Women with BC were randomized to either a control group (standard of care) or to standard of care with a 24-week home-based AE program. Based on our previous feasibility study in this patient population, the graduated exercise program consisted of 2 self-directed sessions per week (performed at 35-85% incremental heart rate reserve intensity) to achieve a minimum of 90 minutes of exercise weekly. Serial transthoracic echocardiography (TTE) was conducted to assess cardiovascular systolic and diastolic function, including strain parameters. Peak oxygen uptake (VO2 max) was estimated using predictive equations based on duration on Bruce protocol treadmill. Quality of life was measured using Functional Assessment of Cancer Therapy – Breast questionnaire. All outcome measurements were performed at baseline and at 24-weeks.
Results: A total of 15 women with BC (49 ± 10 years old) were recruited and randomized to either control (n=7) or AE (n=8). A total of 14 patients received adriamycin and cyclophosphamide for 8 weeks and 1 patient received fluorouracil, epirubicin, and cyclophosphamide for 9 weeks. Additionally, 13 patients received adjuvant radiation therapy. A total of 11 women had baseline cardiovascular risk factors including hypertension (n=1), hyperlipidemia (n=2), smoking history (n=4), and family history of premature coronary artery disease (n=4). The characteristics of patients in the two groups were similar. Participants randomized to AE demonstrated an average of 92% adherence to the program. There were no significant differences between the two groups in the measured cardiovascular morphological or functional parameters. At baseline, mean LVEF was 62±2% in the control group and 63±2% in the AE group. At 24-weeks, mean LVEF was 62±3% and 58±8% in the control and exercise groups, respectively (p = NS). Additionally, at baseline, mean global longitudinal strain (GLS) was -19.5±1.5% in the control group and -19.0±1.2% in the AE group. At 24-weeks, mean GLS was -18.2±1.3% in the control group and -17.5±2.3% in the AE group (p = NS). Further, while VO2 max was 30.1 mL/kg/min for both groups at baseline, it was 33.6 mL/kg/min and 36.3 mL/kg/min at 24-weeks for control and exercise groups, respectively (p = NS). Finally, the FACT-B quality of life scores were not statistically different for both groups at both time points.
Conclusion: These findings indicate that although a 24-week home-based AE program was feasible, we were unable to demonstrate cardioprotection in women with BC receiving chemotherapy in comparison to standard of care.
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Keywords
Exercise, Home-based exercise, Cardiotoxicity, Anthracycline, Breast cancer