A pilot study to evaluate response and angiogenesis after treatment with bevacizumab in patients with inflammatory breast cancer

Abstract

578 Background: Inflammatory breast cancer (IBC) is an aggressive form of breast cancer associated with vascular and lymphatic invasion. Previously untreated IBC patients received bevacizumab (BV), a recombinant humanized monoclonal antibody to VEGF, to evaluate endothelial cell proliferation (CD31/Ki67), tumor cell proliferation (Ki67), tumor microvessel density (MVD), VEGF, and vascular permeability (k21) on dynamic contrast enhanced MRI (dMRI). Methods: Treatment consisted of BV alone for cycle (C) 1 (15mg/m2 on day 1) followed by six cycles of BV (15mg/m2) with doxorubicin (50mg/m2) and docetaxel (75mg/m2) q3wk and G-CSF in C2–7. Following mastectomy and radiation, BV was given for eight more cycles with hormonal therapy for ER+ pts. Tumor core biopsies and dMRI were obtained at baseline, after C1, 4, 7. Results: Sixteen pts enrolled received 125 cycles of treatment. Pts: Stage III 87.5% and IV 12.5%, ER+ 38%, Her2 positive 12.5%. Post-chemo, thirteen pts (3 too early to evaluate): 8PRs, 1PR unconfirmed, 1PD. A decrease in CD31/Ki67 was seen after BV treatment alone (-1% median change, p=0.031). There were no decreases in Ki67 or MVD after BV alone (p=0.97 and 0.70) or BV and chemotherapy (p=0.23 and 0.85). There were significant decreases in k21 after treatment (n=12), with a median change of -53% (p=0.019) after C1, -70% (p=0.001) after C4, and -56% (p=0.008) after C7. In patients with PR there were trends towards a decrease in VEGF after C1(-57% median change, p=0.09) and decrease in Ki67 after C4/C7 (-57% median change, p=0.09). There were no correlations between k21and CD31/Ki67 index, Ki67, or VEGF after BV alone (n=11); but a trend towards a correlation between VEGF and k21 after BV and chemotherapy (r=0.62, p=0.10). Most common grade 3/4 toxicities (n=16): neutropenia (63%), diarrhea (25%), HTN (25%), and febrile neutropenia (19%). Conclusions: Preliminary results revealed a decrease in vascular permeability on dMRI and endothelial cell proliferation with BV treatment alone. In responding pts, there were trends toward a decrease in VEGF after BV and tumor cell proliferation after BV and chemotherapy. No significant financial relationships to disclose.