Effects of exercise training on cardiac toxicity markers in women with breast cancer undergoing chemotherapy with anthracyclines: a randomized controlled trial

Abstract

Aims: Exercise training has been suggested to prevent anthracycline-related cardiac dysfunction, but clinicalbased evidence is scarce. We investigated the effects of a supervised exercise training programme (SETP) on cardiac toxicity markers in women with breast cancer (BC) receiving anthracycline-containing chemotherapy.

Methods and results: Ninety-three women with early-stage breast cancer were randomly allocated to a supervised exercise training programme (SETP) plus usual care group (Exercise, n = 47) or usual care alone group (UC, n = 46). The SETP consisted of three sessions per week, combining aerobic and resistance training, conducted concurrently across the anthracycline-containing chemotherapy length. The primary endpoint was the change in left ventricular ejection fraction (LVEF) from baseline to the end of anthracycline cycles. Secondary endpoints included global longitudinal strain (GLS) and other conventional echocardiographic parameters, cardiorespiratory fitness (estimated peak VO2), circulating biomarkers (NT-proBNP, hs-TnT), and safety of the SETP. The study endpoints were also assessed 3 months after the end of anthracycline cycles. All patients were prescribed four cycles of doxorubicin plus cyclophosphamide (AC). No significant between-group differences in LVEF change were seen at the end of AC [mean difference: 0.7%; 95% confidence interval (CI): -0.8, 2.3; P = 0.349] and 3 months after AC (1.1%; 95% CI: -0.5, 2.6; P = 0.196). Compared to the usual care (UC) group, the estimated peak VO2 increased in the Exercise group at the end of AC (1.6 mL O2·kg-1·min-1; 95% CI: 0.06, 3.1; P = 0.041) and 3 months after AC (3.1 mL O2·kg-1·min-1; 95% CI: 1.4, 4.7; P < 0.001). No between-group differences were found in the remaining secondary endpoints. No serious adverse events were observed during SETP.

Conclusion: Exercise training was safe during chemotherapy and significantly improved cardiorespiratory fitness. No significant effects were seen on cardiac toxicity markers (LVEF or GLS) as compared to the usual care.

Trial registration: Mama Move Gaia on treatment trial ISRCTN32617901.

Keywords: Anthracyclines; Breast cancer; Cardiac toxicity; Exercise training.