Abstract 3279: Nab-paclitaxel and bevacizumab treatment in new models of inflammatory breast cancer, SUM149-RR and SUM149-GL
Authors: Volk Lisa , Wilber Andrew , Desai Neil , Trieu Vuong , Ran Sophia 
Published: February 2011

Background: Inflammatory breast cancer (IBC) is a one of the most lethal forms of breast cancer with a 5-year survival of 40%. The hallmarks of IBC include skin redness, irritation, swelling, pain, as well as extensive lymph nodes (LN) and hematogenous metastasis. Animal models are highly desirable for studying the IBC pathology and for designing therapies that increase patient survival. Here we established and characterized two luciferase- and fluorescently-labeled lines derived from the human IBC line, SUM149. We characterized the growth and metastasis of these lines in vivo as well as their sensitivity to the novel drug combination, nab-paclitaxel and bevacizumab.

Methods: SUM149 cells were stably transfected with Red Fluorescent Protein (RFP) and Renilla luciferase to establish dual reporter termed RR (RFP and Renilla luciferase), or infected with lentivirus encoding Green Fluorescent Protein (GFP) and Firefly luciferase termed GL (GFP and Firefly Luciferase). The new cell lines (SUM149-RR and SUM149-GL) were characterized in vitro and in vivo after orthotopic implantation into mammary fat pads of immunodeficient mice. SUM149-RR was also examined for sensitivity to nab-paclitaxel alone or in combination with bevacizumab. Mice bearing tumors of 150mm3 in size were treated with saline (control), bevacizumab (4mg/kg i.p., twice a week, for 10 weeks), nab-paclitaxel (10mg/kg, i.v., qdx5), or the combination. Tumor growth was monitored by calipers. 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. Bevacizumab alone decreased tumor progression at later but not early stages of tumor growth. Nab-paclitaxel alone inhibited tumor growth by 73%. Combination therapy increased inhibition to 96%, and resulted in 22% (2/9) complete responses. SUM149-RR tumors in control mice displayed ulcerations, edema and redness much like the clinical disease. Tumors in mice treated with bevacizumab or combination therapy showed no signs of inflammation. 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 for human IBC that allow organ visualization and accurate quantification of metastasis. These models can be used for better understanding of the IBC biology and for developing new therapies tailored to specific pathology of this cancer. Preliminary studies demonstrated high sensitivity of SUM149-RR to nab-paclitaxel/bevacizumab therapy suggesting the potential usefulness for treatment of IBC patients.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3279.