Bevacizumab in the treatment of breast cancer: rationale and current data

Vascular endothelial growth factor (VEGF) has emerged as a key target for the treatment of cancer. As the ligand to the VEGF receptor, it plays a central role in promoting tumor angiogenesis. Overexpression of VEGF leads to poor outcomes in patients with breast cancer and other tumors. Preclinical studies have shown that the humanized monoclonal antibody to VEGF, bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA), can reduce tumor angiogenesis and inhibit the growth of solid tumors, either alone or in combination with chemotherapy. As a single agent or added to vinorelbine, bevacizumab has produced encouraging results in phase II clinical trials in patients with refractory metastatic breast cancer. When added to capecitabine chemotherapy in a phase III trial, bevacizumab produced a greater response rate, but did not prolong progression-free survival. This may reflect the late disease stage and poor prognostic factors in the patient population. A large, ongoing, phase III, cooperative group trial is evaluating the effect of bevacizumab in combination with paclitaxel as first-line therapy for metastatic disease. The adverse effect profile of bevacizumab differs from that of cytotoxic chemotherapy and includes hypertension, proteinuria, thrombosis, and epistaxis.