VEGF-targeting therapy for breast cancer.

Vascular Endothelial Growth Factor (VEGF) plays an important role in multiple physiologic and pathologic processes involving endothelial cells. Several preclinical and clinical sources of evidence suggest its importance in human breast cancer. Based on the presumed biologic relevance of VEGF in human breast cancer, clinical trials using agents targeting VEGF were launched beginning in the late 1990s. This clinical trial effort came to fruition in 2005 with the success of the first large, prospective randomized trial of anti-VEGF therapy in patients with front-line metastatic breast cancer, which demonstrated the benefit of adding the monoclonal anti-ligand antibody bevacizumab to the chemotherapeutic agent paclitaxel. Based upon this success, numerous anti-VEGF agents are now being tested in patients with breast cancer, and adjuvant therapy trials are in development. Nevertheless, important questions remain regarding the biology and clinical development of these agents in breast cancer.