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J Am Coll Cardiol, 2007; 50:1435-1441, doi:10.1016/j.jacc.2007.06.037 (Published online 21 September 2007).
© 2007 by the American College of Cardiology Foundation
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STATE-OF-THE-ART PAPER

Early Breast Cancer Therapy and Cardiovascular Injury

Lee W. Jones, PhD*,*, Mark J. Haykowsky, PhD{ddagger}, Jonas J. Swartz, BS*, Pamela S. Douglas, MD{dagger} and John R. Mackey, MD§

* Department of Surgery, Duke University Medical Center, Durham, North Carolina
{dagger} Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina
{ddagger} 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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