Tracking early Cardiotoxicity developed during Chemotherapy in breast Cancer

Abstract

Breast cancer is the most common cancer among women. Existing anti-cancer therapies have improved survival and patient’s quality of live, however, these benefits are often accompanied by cardiotoxicity. Anthracyclines used alone or in combined with trastuzumab lead to a decrease in the left ventricular ejection fraction, often leading to heart failure. This cardiac dysfunction appears to be due to a compensatory increase in sympathetic activity. Physical exercise has been recognized as a strategy to counteract the adverse effects of cancer therapy. Currently, it is not possible to predict which patients will be affected and the methods used are insufficient and insensitive. Also, no reliable early biomarkers of drug-induced cardiac disease have been identified. The objective of this thesis was to develop and functionally characterize a doxorubicin (DOX) animal model and the exercise efficacy to mitigate the adverse cardiovascular effects. For that, healthy female Wistar rats were divided into 3 groups: DOX (ip. 8 mg/kg, once a week for 4 weeks), DOX with exercise training (treadmill, 5x/week) and controls (ip. saline). Physiological, autonomic, echocardiography, behavioural and metabolic evaluation were performed. Results showed that DOX treatment developed bradypnea, anxiety, baroreflex, chemoreflex and cardiac dysfunction, anxiety, but without cardiotoxicity. Exercise training improved anxiety levels, cardiac output, blood pressure, baroreflex gain, respiratory and heart rates compared to non-trained group. These cardiovascular changes might be due to an increase in stroke volume due to longer diastoles as showed by echocardiography, despite total peripheral resistance was not evaluated. However, chemoreflex sensitivity, sympathetic and parasympathetic activities remained similar. Nevertheless, still preliminary and needing complementary autonomic and molecular studies, these findings suggest that lifestyle interventions, namely moderate exercise, can improve cardiovascular health in at risk populations.