Targeting Tumor Angiogenesis in Combination with Endocrine Therapy in Patients with Hormone-Receptor Positive Metastatic Breast Cancer.

PURPOSE In breast cancer, preclinical models suggest that antiangiogenic therapy in combination with antiestrogens may prevent or overcome resistance to endocrine therapy. This review aims to discuss feasibility and phase II studies that have led to ongoing randomized trials of combination treatment with antiangiogenic agents and endocrine therapy. METHODS A systematic search of PubMed and conference databases was performed to identify reports of phase I-III clinical trials investigating combination endocrine therapy with antiangiogenic agents in breast cancer. In addition, results of our feasibility trial of letrozole plus bevacizumab were updated. RESULTS We identified 11 trials that reported data for or are currently evaluating the combination of antiangiogenic agents with endocrine therapy: seven trials evaluated endocrine therapy plus bevacizumab, and four trials evaluated endocrine therapy plus tyrosine kinase inhibitors (TKIs) of vascular endothelial growth factor receptor (VEGFR). Side effects that have emerged from this combination include hypertension (HTN), proteinuria, and ''off-target'' TKI side effects including skin rash and diarrhea. Early efficacy data suggests activity for this combination. CONCLUSION Clinical trials have demonstrated the feasibility of endocrine therapy in combination with antiangiogenic agents. Phase III proof-of-efficacy trials of endocrine plus anti-VEGF therapy are ongoing (CALGB 40503, GEICAM 2006-11/GBG 51). [ABSTRACT FROM AUTHOR]