Clinical data for anti-angiogenic agents in previously treated advanced breast cancer

The vascular endothelial growth factor (VEGF) ligand and its receptor represent key targets for anti-angiogenic agents in the therapy of breast cancer. Such agents include bevacizumab, sunitinib, sorafenib and vandetanib; all of which are currently in clinical development for breast cancer. The most extensively studied of these agents is bevacizumab, and a phase III trial of this agent in combination with capecitabine demonstrated a significant improvement in response rate for the combination regimen compared with capecitabine alone in patients previously treated for metastatic breast cancer. However, the lack of a corresponding significant improvement in progression-free and overall survival may be attributable to the nature of breast cancer tumour progression. Preclinical studies suggest that VEGF may be the predominant pro-angiogenic factor expressed at early disease stages, whereas other angiogenic factors may be more important in advanced disease. Clinical evidence is not yet available, but this theory suggests that bevacizumab may be more effective when used earlier in the course of breast cancer therapy.