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Cardiotoxicity of Novel Cancer Therapies Open Access


Other title
cardiac MRI
cardiopulmonary exercise testing
Type of item
Degree grantor
University of Alberta
Author or creator
Pituskin, Edith
Supervisor and department
Haykowsky, Mark (Rehabilitation Medicine)
Examining committee member and department
Thompson, Richard (Biomedical Engineering)
Campbell, Kristen (Physical Therapy, University of British Columbia)
Paterson, Ian (Medicine, Cardiology)
Mackey, John (Medicine, Oncology)
McNeely, Margaret (Rehabilitation Medicine)
Faculty of Rehabilitation Medicine

Date accepted
Graduation date
Doctor of Philosophy
Degree level
Breast cancer is the most common malignancy among females, and the second leading cause of cancer death among Canadian women. Despite improved survival, both short and long term detrimental effects have been observed with both novel and conventional anti-cancer therapies. In particular, the effects of cancer therapy on the cardiovascular system, or ‘cardiotoxicity’, are increasingly recognized in terms of morbidity and mortality. Subtle or ‘sub-clinical’ early effects of anti-cancer therapies on cardiac structures may remain undetected, conveying potentially devastating longer-term effects. The overarching theme of this thesis is to examine the short and long-term effects of a novel anti-cancer therapy, trastuzumab, on left ventricular (LV) morphology and function in breast cancer patients. Two studies were undertaken; study #1 was a cross-sectional study of 17 female breast cancer survivors exposed to trastuzumab-based chemotherapy, examining LV remodeling and exercise capacity. We found that early breast cancer patients had significant alterations in left ventricular geometry and impairment of cardiorespiratory function four years following exposure to trastuzumab-based chemotherapy. The second study was performed to examine the effects of three months of standard heart failure therapy, consisting of angiotensin-converting enzyme inhibitor or beta-blocker vs placebo, on LV remodeling in breast cancer patients receiving trastuzumab-based therapy. The major finding was that that standard heart failure pharmacotherapy appeared to be effective in attenuating LV dysfunction associated with trastuzumab-based therapy. When compared to patients randomized to the pharmacotherapy group, significant decline in left ventricular ejection fraction occurred in the placebo group.
Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
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