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.

Breast cancer is the most common malignancy in American women, with approximately 213,000 new cases diagnosed in 2006 (1). Although the incidence of breast cancer has increased by 0.2% per year between 1997 and 2000, improvements in detection and therapy have resulted in significant survival gains with breast cancer-specific mortality decreasing almost 24% between 1990 and 2000. As a result, approximately 2.3 million American women are now living with a previous history of breast cancer, with sufficient survival to be at risk for cardiovascular disease (CVD). The purpose of this paper is to review the cardiovascular effects of current and forthcoming adjuvant therapies for the treatment of early breast cancer so that clinicians will be better able to care for this emerging cohort of new cardiovascular patients. We also review the evidence supporting the potential treatment efficacy of conventional cardiovascular risk factors with both drugs and lifestyle modifications, including exercise therapy, to mitigate and/or prevent therapy-induced CVD in this population.