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

Abstract

Background Exercise training has been suggested to prevent anthracycline-related cardiac dysfunction, but clinical-based evidence is scarce. Aim We investigated the effects of a supervised exercise training program (SETP) on cardiac toxicity markers in women with breast cancer receiving anthracycline-containing chemotherapy. Methods Ninety-three women with early-stage breast cancer were randomly allocated to a SETP plus usual care group (Exercise, n=47) or usual care alone group (UC, n=46). The SETP consisted of 3 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. Results 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 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 usual care.

Impact of Aerobic Training on Cardiovascular Function, Fitness, and Patient Reported Outcomes During Anthracycline Chemotherapy: A Case Series in Women With Breast Cancer

“…This study is the first to highlight the individual variation in GLS observed in response to AC treatment and aerobic exercise, although findings are similar to those presented at a group level by Foulkes et al 21 and more recently Antunes et al 39 The same exercise intervention performed in this current study has been shown to improve GLS in women with cardiovascular disease risk factors, 22 which may suggest that other factors, such cumulative AC dose and combination treatment outweigh the potential benefits of aerobic exercise on myocardial function as measured by GLS. Results from this study may also support this suggestion, as after 4-weeks, GLS was improved or maintained from baseline in all participants, potentially indicating an acute positive effect of exercise on GLS.…”

“…Although not an aim of this study, change in VO 2 peak and GLS did not appear to occur in the same direction, which is again similar to findings from recent randomized controlled trials. 21,39 The reduction in VO 2 peak observed in 2 of the 4 exercising participants does not align with literature supporting the use of exercise to maintain or improve aerobic fitness in women with breast cancer undergoing AC chemotherapy. 20 Participant 2, who experienced the greatest reduction in VO 2 peak upon the completion of DDAC, also scored poorer across multiple symptom domains in comparison to the other 3 exercising participants upon the completion of DDAC treatment (Table 4).…”

“…20 However, due to the recruitment challenges described above, this was not achieved, and leaves a gap for future research to explore. While recent randomized controlled trials have investigated the impact of exercise on GLS and CTRCD incidence at a group level in this population, 21,39 additional studies of similar design will assist in the validation of these findings. As the impact of exercise on GLS and asymptomatic CTRCD incidence was varied amongst participants in this study, future research should investigate if different volumes and/ or intensities of exercise that is, up to 5 aerobic exercise sessions per week, or high intensity interval training, have a more consistent impact on GLS and asymptomatic CTRCD incidence.…”

Exercise Training Benefits Health-Related Quality of Life and Functional Capacity during Breast Cancer Chemotherapy: A Randomized Controlled Trial

“…Exercise group: 23%, P = 0.002). The significant benefits observed in maximum voluntary handgrip strength and in the 30-s chair sit-to-stand test, along with the previously reported significant improvement in cardiorespiratory fitness (34), may account for the differences in the number of patients with CMW on the physical functioning domain, between the two groups. In this study, there was also a significant effect of exercise on self-reported cognitive functioning, consistent with the findings from the PACES and OptiTrain trials (35,41).…”

“…Regarding the SETP, the mean adherence to training frequency was 63.2 ± 26.9% (73.8 ± 17.8% considering the 32 patients that remained enrolled during chemotherapy) and no serious adverse events were reported during the training sessions (34). Details regarding the safety and tolerability of the SETP are provided elsewhere (34).…”