Exercise cardio-protection from chemotherapy for breast cancer

One in nine women in Canada will be diagnosed with breast cancer during their lifetime, yet 88% will live for at least five years after diagnosis. Cardiovascular disease has become the most common cause of death of older breast cancer survivors, and breast cancer survivors are more likely to die of cardiovascular disease than women who have not had breast cancer. One of the contributing factors to the increased cardiovascular morbidity and mortality is anthracycline chemotherapy-related cardiotoxicity, or damage to the myocardium. The need for balance of oncological efficacy with cardiotoxicity of anthracycline chemotherapy has driven the active investigation of cardio-protective strategies. Exercise, an accessible and inexpensive intervention with numerous other health benefits, has demonstrated efficacy for attenuating cardiotoxicity in numerous preclinical (i.e. animal model) studies; a finding yet to be confirmed by clinical research. This dissertation investigated the potential for exercise cardio-protection from anthracycline chemotherapy in women diagnosed with breast cancer in three studies. The primary findings are: 1) during anthracycline treatment, adherence to supervised exercise training following the guidelines for cancer survivors varies widely; 2) the primary reason for withdrawal, missed exercise sessions, and non-adherence to prescribed intensity and/or duration was treatment-related symptoms; 3) despite low and variable adherence, women who enrolled in an exercise training program during anthracycline chemotherapy for breast cancer did not experience a clinically relevant deterioration of echocardiography-derived systolic global longitudinal strain or strain rate, which are both established predictive markers of cardiotoxicity; 4) global longitudinal strain has excellent intra-observer reliability and is consistently measurable in breast cancer patients, making it an excellent option for an outcome measure to assess cardio-protection; 5) performance of a single vigorous intensity aerobic exercise bout performed 24 hours prior to anthracycline treatment attenuates the acute NT-proBNP myocardial injury marker response to the first treatment, and alters hemodynamic regulation and cardiac structure after completion of treatment, but has no effect on longitudinal strain or strain rate or treatment symptoms. Overall this dissertation provides proof-of-principal for exercise cardio-protection, and contributes novel findings regarding exercise prescription and outcome measure assessment for future exercise cardio-protection studies during anthracycline treatment for breast cancer.Medicine, Faculty ofGraduat