Abstract 647: Xenograft Models of Breast Cancer: the Link between Characteristics of Biomarker Expression and the Anti-tumor Effect of the Representative Therapies

Abstract

Gene expression analysis has led to the identification of 5 subtypes of breast cancer (basal-like, HER2-like, luminal A and B, and normal-like) that have distinct biological features, clinical outcomes, and responses to conventional chemotherapy and targeted therapy. Animal models possessing genetic and other biomarker abnormalities similar to each subtype of the human counterpart are thus of crucial importance in the development of new therapeutic strategies. Human breast cancer xenograft model is one of the more difficult models with transplantation of either established cell lines or primary tumors. We have successfully established 6 xenograft models derived from established cell lines and 2 xenograft models by transplanting primary human tumor fragments. The immunohistochemical results classified the 9 models into 4 major groups: ER negative and HER2 negative (MX-1, MDA-MB-231, MCF-7-CB1, and SKBR3-CB1), ER negative and HER2 positive (BT-474-CB1), ER positive and HER2 negative (MCF-7), and ER positive and HER2 positive (BT-474), which well resembled basal-like/normal-like, HER2-like, luminal A, and luminal B breast cancer types in human. The mutation status of TP53, BRCA1, BRCA2 and EGFR was investigated, and compared with the in vivo efficacy results by using various test drugs including cytotoxic agents, paclitaxel and doxorubicin; ER antagonist, tamoxifen; anti-HER2 monoclonal antibody, trastuzumab; HER2 inhibitor, HKI-272 and EGFR inhibitor, erlotinib. These data closely mimicked the heterogeneity in clinical outcomes of the human disease. Therefore, these models provide valuable platform for the development of personalized therapy for breast cancer. 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 647.