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STATE-OF-THE-ART PAPER

Early Breast Cancer Therapy and Cardiovascular Injury

Lee W. Jones, PhD^_*,_*, Mark J. Haykowsky, PhD, Jonas J. Swartz, BS^_*, Pamela S. Douglas, MD and John R. Mackey, MD

^_* Department of Surgery, Duke University Medical Center, Durham, North Carolina
Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina
Faculty of Rehabilitation Medicine, Division of Medical Oncology, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada
Faculty of Medicine, Division of Medical Oncology, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada.

Manuscript received April 11, 2007; revised manuscript received May 24, 2007, accepted June 3, 2007.

^_* Reprint requests and correspondence: Dr. Lee W. Jones, Box 3624, Duke University Medical Center, Durham, North Carolina 27710. (Email: lee.w.jones{at}duke.edu).

Although recent advances in curative-intent therapies are beginning to produce significant survival gains in early breast cancer, these improvements may ultimately be attenuated by increased risk of long-term cardiovascular mortality. This paper reviews emerging evidence on the cardiovascular effects of breast cancer adjuvant therapy and proposes a new entity that we have labeled the "multiple-hit" hypothesis. The evidence that lifestyle modification, especially exercise therapy, may mitigate these adverse effects is also reviewed. These issues are of considerable practical importance for cardiovascular clinicians, as identification and intervention in those at high risk for cardiovascular complications may reduce a major cause of mortality in women with early breast cancer.

Abbreviations and Acronyms   ACEI = angiotension-converting enzyme inhibitor   CVD = cardiovascular disease   EPC = endothelial progenitor cell   ER = estrogen receptor   HER = human epidermal growth factor receptor   HF = heart failure   LVEF = left ventricular ejection fraction   ROS = reactive oxygen species

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