[Application of bevacizumab on metastatic breast cancer]

Tumor angiogenesis defines tumor growth as it is dependent on generation of new blood vessels. Over forty years ago, Folkman hypothesized that inhibiting tumor angiogenesis could inhibit the growth of solid tumors and thus could be exploited as a therapeutic strategy. Among the numerous factors have been implicated in the angiogenesis activation process, vascular endothelial growth factor (VEGF) is the best studied angiogenesis target in cancer, using many different approaches in a wide variety of human cancers. Bevacizumab is the first anti-VEGF monoclonal antibody and proof-of-concept angiogenesis inhibitor that has been approved by the United States FDA for several tumor types. Drugs inhibiting VEGF work through several mechanisms, including inhibition of tumor blood vessel growth, vascular renormalization, potentiating of other antitumor agents, and inhibiting tumor metastasis. Unlike colorectal, kidney, lung, and brain tumors, the use of bevacizumab in breast cancer has been, as it were, on a rollercoaster in the United States, from accelerated approval for early drug access by patients in February 2008, to modest efficacy that fell short of high expectations, and increasing concern for serious toxicity in July 2010, and on to FDA revocation of accelerated approval for metastatic breast cancer patients in November 2011. Through a concise review of the FDA process, we have summarized its lessons, the challenges in developing new cancer drugs, and perspectives on further development of bevacizumab and other angiogenesis inhibitors in treatment of breast cancer. Despite all the challenges, antiangiogenesis remains a promising strategy to conquer breast cancer.