Bevacizumab to Treat Inflammatory Breast Cancer or Locally Advanced Breast Cancer

This is a pilot study in patients with previously untreated inflammatory breast cancer (IBC) or locally advanced breast cancer (LABC) to evaluate angiogenesis parameters after treatment with rhuMAb VEGF - recombinant humanized monoclonal antibody vascular endothelial growth factor (bevacizumab). The challenge for new molecular-targeted anti-angiogenesis therapy is to devise appropriate and reliable markers to monitor efficacy. This may be achieved directly by evaluating changes in angiogenesis parameters in tumor samples. The use of less invasive surrogate markers to assess the efficacy of anti-angiogenic therapy is preferable. This may include functional changes in tumor vasculature assessed using non-invasive methods such as magnetic resonance imaging (MRI) or determination of changes in circulating soluble markers of angiogenesis. Most breast cancers over express VEGF thus making it an ideal disease for treatment with anti-angiogenesis therapy. This study will evaluate the effects of bevacizumab on angiogenesis parameters both molecular and functional. The first cycle will consist of bevacizumab alone followed by six cycles of bevacizumab in combination with doxorubicin and docetaxel (AT). Loco-regional therapy will follow and bevacizumab will be recommenced for eight cycles. Changes in pre-designated angiogenesis parameters will be assessed at baseline, three weeks after bevacizumab and after three cycles of AT/bevacizumab. The first three molecular parameters: endothelial cell proliferation, endothelial cell apoptosis and tissue VEGF require multiple tumor core biopsies obtained using a mammotome. The fourth parameter k(ep), the redistribution constant is obtained using dynamic MRI. To determine the variability of the values of the three molecular primary angiogenesis parameters, multiple biopsies will be sampled at the same time points. An attempt will be made to correlate each of the four primary angiogenesis parameters with time to progression/recurrence. The effects of bevacizumab alone and AT/bevacizumab directly on tumor vasculature using dynamic MRI imaging and on the circulating angiogenesis marker, serum vascular cell adhesion molecule-1 (VCAM-1) at the same three time points and prior to surgery and will be undertaken in an exploratory manner. An attempt will be made to correlate changes in these parameters with clinical findings and changes in tissue angiogenesis parameters. Additionally, other angiogenesis biomarkers will also be studied in an exploratory manner. Thrombosis factors will be monitored given the increased incidence of venous and arterial thrombosis seen in previous clinical trials using bevacizumab. An increase in the incidence of hypertension has also been seen. A subset of patients in this study will undergo frequent blood pressure monitoring to obtain a profile of the effect of bevacizumab on blood pressure.