Abstract P1-03-09: Combination of nab-Paclitaxel and Bevacizumab Inhibited Tumor Growth and Metastasis of New Inflammatory Breast Cancer Models

Abstract

Abstract Background: Inflammatory breast cancer (IBC) is a highly lethal form of breast cancer which is characterized by skin redness, irritation, swelling, pain, as well as extensive lymph nodes (LN) and hematogenous metastasis. Animal models of IBC are highly desirable for studying its pathology and for designing effective therapies. In this study, we established two new luciferase-and fluorescently-labeled IBC models and tested the efficacy of the novel drug combination nab-paclitaxel and bevacizumab. Methods: Inflammatory SUM149 breast cancer cells were stably transfected with Red Fluorescent Protein (RFP) and Renilla luciferase to establish SUM149-RR, or infected with lentivirus encoding Green Fluorescent Protein (GFP) and Firefly luciferase to establish SUM149- GL. The new cell lines were characterized both in vitro and in vivo. Immunodeficient mice bearing SUM149-RR tumors of 150mm3 in size were treated with saline (control), bevacizumab (4 mg/kg, i.p., twice a week, for 10 weeks), nab-paclitaxel (10 mg/kg, i.v., qdx5), or the combination. Metastasis was analyzed by measuring luciferase activity in the lymph nodes (LN) and lungs. Results: Luciferase measurements and in vivo imaging showed that both SUM149-RR and-GL clones were highly metastatic to LN, lungs, liver, brain, and spleen. SUM149-RR tumors in control mice displayed ulcerations, edema and redness similar to the clinical disease, while tumors in mice treated with bevacizumab or combination therapy showed no signs of inflammation. Bevacizumab alone decreased tumor growth at later but not early stages of tumor growth, whereas nab-paclitaxel alone inhibited tumor growth by 73%. Combination therapy increased inhibition to 96%, and resulted in 22% (2/9) complete responses. Histologically, tumors from bevacizumab treated groups were more morphologically intact with reduced vascular abnormalities than tumors from control or nab-paclitaxel treated mice. LN and lung metastasis was significantly reduced in all treated groups as compared with control. Conclusions: The SUM149-RR and SUM149-GL lines are new double-tagged models of human IBC that allow organ visualization and accurate quantification of metastasis. These models can be used to study the biology and treatment of IBC. Combination of nab-paclitaxel with bevacizumab was highly effective against SUM149-RR, suggesting the potential usefulness of this regimen for treatment of IBC patients. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-03-09.