Antiangiogenic and antitumor effects of bevacizumab in patients with inflammatory and locally advanced breast cancer

Purpose Vascular endothelial growth factor (VEGF) is a potent molecule that mediates tumor angiogenesis primarily through VEGF receptor 2 (VEGFR2). Bevacizumab, a recombinant humanized monoclonal antibody to VEGF, was administered to previously untreated patients to evaluate parameters of angiogenesis. Patients and Methods Twenty-one patients with inflammatory and locally advanced breast cancer were treated with bevacizumab for cycle 1 (15 mg/kg on day 1) followed by six cycles of bevacizumab with doxorubicin (50 mg/m(2)) and docetaxel (75 mg/m(2)) every 3 weeks. After locoregional therapy, patients received eight cycles of bevacizumab alone, and hormonal therapy when indicated. Tumor biopsies and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) were obtained at baseline, and after cycles 1, 4, and 7. Results A median decrease of 66.7% in phosphorylated VEGFR2 (Y951) in tumor cells (P =.004) and median increase of 128.9% in tumor apoptosis (P =.0008) were seen after bevacizumab alone. These changes persisted with the addition of chemotherapy. There were no significant changes in microvessel density or VEGF-A expression. On DCE-MRI, parameters reflecting reduced angiogenesis, a median decrease of 34.4% in the inflow transfer rate constant (P =.003), 15.0% in the backflow extravascular- extracellular rate constant (P =.0007) and 14.3% in extravascular-extracellular volume fraction (P =.002) were seen after bevacizumab alone. Conclusion Bevacizumab has inhibitory effects on VEGF induces apoptosis in tumor cells.