Background: Anthracyclines are chemotherapeutic agents frequently used in breast cancer (BC) treatment. Although it improves 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 anthracycline-related cardiotoxicity (ARC). Most of the data on the effects of exercise to reduce ACT are from animal studies, with only a few studies in a limited number of patients indicating beneficial effects. To better understand the effectiveness of exercise in the mitigation of ARC, clinical, real-world trials claim require a larger sample size and more accurate and valuable clinical biomarkers. In this study, we intend to include a large sample and investigate cardiac function through serial measures of biomarkers and imaging techniques.
Methods: This protocol describes a two-arm, 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 recommended 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 receive 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 3 months after t2 (t3). Additionally, NT-proBNP will be measured 1-24 h 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.
Keywords: Breast cancer; Cardiac healthcare; Cardiotoxicity; Supervised exercise; Supportive cancer care.