The Beneficial Role of Physical Exercise on Anthracyclines Induced Cardiotoxicity in Breast Cancer Patients

The increase in breast cancer (BC) survival has determined a growing survivor population that seems to develop several comorbidities and, specifically, treatment-induced cardiovascular dis-ease (CVD), especially those patients treated with anthracyclines. Indeed, it is known that these compounds act through the induction of supraphysiological production of reactive oxygen species (ROS), which appear to be central mediators of numerous direct and indirect cardiac adverse consequences. Evidence suggests that physical exercise (PE) practised before, during or after BC treatments could represent a viable non-pharmacological strategy as it increases heart tolerance against many cardiotoxic agents, and therefore improves several functional, subclinical, and clinical parameters. At molecular level, the cardioprotective effects are mainly associated with an exercise-induced increase of stress response proteins (HSP60 and HSP70) and antioxidant (SOD activity, GSH), as well as a decrease in lipid peroxidation, and pro-apoptotic proteins such as Bax, Bax-to-Bcl-2 ratio. Moreover, this protection can potentially be explained by a preservation of myosin heavy chain (MHC) isoform distribution. Despite this knowledge, it is not clear which type of exercise should be suggested in BC patient undergoing anthracycline treatment. This highlights the lack of special guidelines on how affected patients should be managed more efficiently. This review offers a general framework for the role of anthracyclines in the physio-pathological mechanisms of cardiotoxicity and the potential protective role of PE. Finally, potential exer-cise-based strategies are discussed on the basis of scientific findings