Impact of exercise training on cardiotoxicity and cardiac health outcomes in women with breast cancer undergoing anthracycline-containing chemotherapy: a study protocol for a randomized controlled trial.

Background: Anthracyclines are chemotherapeutic agents frequently used in breast cancer (BC) treatment. Although improving disease-free and overall survival, the use of anthracyclines is associated with a cumulative risk of cardiac toxicity. Preventive strategies to optimize cardiac health are needed and exercise is proposed as a potential non-pharmacological approach for counteracting of anthracycline-related cardiotoxicity (ARC). Most of the data on the effects of exercise to reduce ACT is from animal studies, with only a few studies with a limited number of patients indicating beneficial effects. To better understand the effectiveness of exercise in mitigation of ARC, clinical, real-world trials claim for a larger sample size and more accurate and valuable clinical biomarkers. In this study, we intend to include a large sample size and investigate cardiac function throughout serial measures of biomarkers and imaging techniques. Methods: This protocol describes a two-armed prospective randomized controlled trial that will explore the cardioprotective effect of a structured exercise program in women with BC undergoing anthracycline-containing chemotherapy (ACT). Ninety adult women with early BC and with a therapeutic decision to receive ACT will be randomly assigned (1:1) to an intervention group or a control group. Patients allocated to the intervention group will perform a supervised exercise program three times per week, consisting of a combination of aerobic and resistance training with progressive intensity and volume, during the time period they received ACT. The control group will receive standard BC care. Primary outcomes related to cardiac (dys)function will be circulating N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, resting left ventricular (LV) longitudinal strain, and resting LV ejection fraction. Secondary outcomes will include the assessment of resting blood pressure, resting heart rate (HR), resting HR variability (HRV), recovery HR, physical function outcomes, self-reported physical activity level, health-related quality of life and fatigue. Data will be obtained at baseline (t0), after the end of anthracycline-treatment (t2), and three months after t2 (t3). Additionally, N-terminal pro-brain natriuretic peptide levels will be measured 1-24 hours prior to each anthracycline-treatment cycle (t1). Discussion: The implementation of the present study design, using novel clinical biomarkers, will determine the effect of structured exercise interventions at mitigating ARC, with the overall aim of finding means to further improve BC care. Trial registration: ISRCTN, ISRCTN32617901. Registered on 24 October 2018. Last updated on 11 January 2019, https://doi.org/10.1186/ISRCTN32617901.