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Cardiotoxicity of Novel Cancer Therapies

  • Author / Creator
    Pituskin, Edith
  • 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.

  • Subjects / Keywords
  • Graduation date
    2013-11
  • Type of Item
    Thesis
  • Degree
    Doctor of Philosophy
  • DOI
    https://doi.org/10.7939/R3SQ8QV05
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
    English
  • Institution
    University of Alberta
  • Degree level
    Doctoral
  • Department
    • Faculty of Rehabilitation Medicine
  • Supervisor / co-supervisor and their department(s)
    • Haykowsky, Mark (Rehabilitation Medicine)
  • Examining committee members and their departments
    • Paterson, Ian (Medicine, Cardiology)
    • Mackey, John (Medicine, Oncology)
    • McNeely, Margaret (Rehabilitation Medicine)
    • Campbell, Kristen (Physical Therapy, University of British Columbia)
    • Thompson, Richard (Biomedical Engineering)