Integrating bevacizumab into the treatment of patients with early-stage breast cancer: focus on cardiac safety.

Significant advances have been made in the treatment of patients with breast cancer in recent years. As increasing numbers of patients become long-term survivors, there must be a greater focus on treatment-induced chronic toxicities, such as left ventricular dysfunction, congestive heart failure (CHF), and/or secondary treatment malignancies. More recently, the HER2-targeted monoclonal antibody (MoAb) trastuzumab has been found to increase the risk for CHF, particularly when used in combination with an anthracycline or in anthracycline-pretreated patients. In early-stage breast cancer, CHF has been reported in up to 4% of trastuzumab-treated, anthracycline-pretreated patients. Given this background, the clinical development of bevacizumab, a MoAb to vascular endothelial growth factor, is proceeding--with careful consideration given to cardiac safety--in this setting. Cardiac toxicity has been reported in association with bevacizumab-based therapy in patients with advanced or metastatic breast cancer, many of whom were previously exposed to anthracyclines. Although there is currently little evidence to suggest that bevacizumab increases the risk or worsens the severity of cardiac events in these patients, it is anticipated that ongoing, well-designed prospective trials will fully evaluate the cardiac safety of bevacizumab in patients with early-stage breast cancer. This review analyzes the cardiac safety profile of bevacizumab in breast cancer, with a focus on early-stage disease, and the ongoing clinical development of this important new drug.