Basic Science for Clinicians Modulation of Anthracycline-Induced Cardiotoxicity by Aerobic Exercise in Breast Cancer Current Evidence and Underlying Mechanisms

Anthracycline-containing chemotherapy (eg, doxorubicin) is well known to cause dose-dependent, progressive cardiac damage clinically manifest as decreased left ventricular (LV) ejection fraction and, ultimately, heart failure (HF) (Table 1).1,2 Unfortunately, the only clinically accepted method to minimize injury is dose modification and/or therapy discontinuation.3 An important current challenge in breast cancer management is therefore to maximize the benefits of doxorubicin while minimizing cardiac damage. Identification and examination of new interventions to prevent and/or treat doxorubicin-induced cardiotoxicity are urgently required. Aerobic exercise is a nonpharmacological therapy that promises to attenuate doxorubicin-induced cardiotoxicity. Aerobic exercise is well documented to improve systolic and diastolic function and attenuate pathological cardiac remodeling, resulting in improved exercise tolerance and resistance to fatigue during exertion in patients with HF.4,5 The cardioprotective properties of aerobic exercise in the context of doxorubicin have, in contrast, received scant attention. It is not generally used in cancer patients despite its lack of “side effects” and the paucity of alternative strategies to prevent/ treat doxorubicin-associated cardiac damage. As a first step in the possible use of exercise in cancer patients, we reviewed the mechanisms of doxorubicininduced cardiotoxicity and the available evidence supporting the utility of aerobic exercise to prevent/treat cardiac injury. We also explored the molecular mechanisms that may underlie the cardioprotective properties of aerobic exercise. These findings have implications for future research regarding the application and effectiveness of exercise and doxorubicin treatment in humans.