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

Abstract

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 (t 0 ), after the end of anthracycline-treatment (t 2 ), and 3 months after t2 (t 3 ). 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. Electronic supplementary material The online version of this article (10.1186/s13063-019-3499-9) contains supplementary material, which is available to authorized users....

Effects of Exercise on Cardiac Function Outcomes in Women Receiving Anthracycline or Trastuzumab Treatment for Breast Cancer: A Systematic Review and Meta-Analysis

“…Therefore, additional research is needed to identify a safe and optimal dose of FITT (frequency, intensity, time, type) prescription to target this issue. We identified ten ongoing trials [27,36] and four published study protocols [37][38][39][40] which are exploring this topic and their results might help to address some research gaps in a near future.…”

“…Four unique RCTs [23][24][25][26] were included (Table 1). Furthermore, we identified ten ongoing trials [27][28][29][30][31][32][33][34][35][36] and four published study protocols [37][38][39][40] that appear to meet the predefined PICO criteria (Supplementary Material Table S2).…”

Exercise to Reduce Anthracycline-Mediated Cardiovascular Complications in Breast Cancer Survivors

“…In fact, the primary prescription of RT within the literature, to date, is exclusively coupled with AE. Moreover, it is hypothesized that an exercise program consisting of a combined prescription of both AE and RT may induce favorable physiological outcomes when compared to either modality prescribed independently [57][58][59]. To evaluate the application of combination training in BC populations, a randomized controlled trial by Cornette et al sought to investigate the effects of a two-arm prospective home-based exercise program consisting of both aerobic and RT prescribed to a BC population (Table 4).…”

Physical Activity as an Imperative Support in Breast Cancer Management

“…Furthermore, another clinical trial (ISRCTN32617901) is currently taking place to demonstrate the impact of PA (3 days per week with progressive volume and intensity during the period of treatment) on anthracycline-derived cardiotoxicity medical care. Multiple variables will be studied, including biochemical, physiological, and psychological parameters [ 161 ]. Even from an acute dose, PA seems to prevent and improve cardiovascular function prior to chemotherapy, as demonstrated by Kirkham et al [ 162 ], who observed a wide multitude of positive effects of 30 min duration PA only 24 h before doxorubicin treatment, including echocardiographic, serological, and physiological parameters.…”