Abstract 3852: Combination treatment of nab-paclitaxel and bevacizumab in a new model of triple-negative breast cancer
Authors: Volk Lisa , Boral Debasish , Wilber Andrew , Desai Neil , Trieu Vuong , Ran Sophia 
Published: February 2011

Background: Tumors that lack estrogen, progesterone, and Her2/nu (triple-negative) are one of the most aggressive, therapy-resistant and highly metastatic subtypes of breast cancer (BC). Most currently available models do not recapitulate expression profile of triple-negative BC, thus making it difficult to devise new treatments that target this tumor type. Here, we established and characterized a new model of triple-negative BC. We also tested the novel combination of nab-paclitaxel with bevacizumab, which has been successful in treating other metastatic cancer types.

Methods: HCC1806 cells were obtained stably transfected with Red Fluorescent Protein (RFP) and Renilla luciferase to establish dual reporter termed RR (RFP and Renilla luciferase). The new derivative was designated as HCC1806-RR and characterized in proliferation and cytotoxicity assays. HCC1806-RR was also orthotopically implanted into mammary fat pads of immunodeficient mice to determine tumor cell sensitivity to chemotherapy alone or in combination with anti-VEGF-A antibody. Mice bearing orthotopic HCC1806-RR 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 with combination of nab-paclitaxel and bevacizumab. Tumor growth rate was monitored by using calipers. Metastasis was analyzed by measuring luciferase activity in the lymph nodes (LN) and lungs.

Results: The parental HCC1806 and its derivative HCC1806-RR had identical morphology, proliferation rates and sensitivity to nab-paclitaxel. Luciferase measurements and imaging in vivo showed that HCC1806-RR tumors have predominant LN metastasis with lungs being a second metastatic site. Bevacizumab and nab-paclitaxel inhibited tumor growth by 0% and 90%, respectively. Combination therapy inhibited tumor growth by 100%. This result was highly significant compared with either control (P &lt; 0.001) or nab-paclitaxel (P = 0.024) group. Importantly, only combination therapy reduced incidence of LN and lung metastases by 50% and 87%. This result was statistically significant as compared with all other groups, with P-values of 0.007 and 0.001 for LN and pulmonary metastases, respectively. Half of the mice in the combination therapy group (n =10) had complete regressions of primary tumors and metastases at both regional and distant sites.

Conclusions: The HCC1806-RR is a new model double-tagged with RFP and Renilla luciferase. These tags allow for quantitative assessment of metastatic spread. This model can be used to study the biology of triple-negative breast cancer and for designing new approaches to treat this type of cancer. Preliminary studies demonstrated high sensitivity of HCC1806-RR to nab-paclitaxel combined with bevacizumab suggesting that this therapy could significantly improve the health outcome for patients with triple-negative breast cancers.

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 3852.