Abstract 1198: Conversion of triple negative breast cancer cells into HER2 positive cells - a novel therapeutic approach

Abstract

Abstract Introduction: Triple negative breast cancer (TNBC) is defined by the lack of estrogen-receptor alpha (ERα) and progesterone receptor (PGR) expression as well as absence of human epidermal growth factor receptor2 (HER2/neu) overexpression. This type of breast cancer is characterized by a poor prognosis and significantly reduced survival rate compared to other breast cancer subtypes. This is mostly due to the lack of targeted agents like endocrine or anti HER2 targets. Breast cancers which express HER2 are usually treated by chemicals targeting the human epidermal growth factor receptor; either by blocking the extracellular domain of HER2 through trastuzumab or the intracellular domain of HER2 through the small molecule lapatinib. Both therapeutics lead to inhibition of downstream signaling pathways like MAPK and PI3K signaling, resulting in increased apoptosis as well as reduced proliferation. Methods: We hypothesize that downstream effects e.g. reduced proliferation or apoptosis might be induced in triple negative breast cancer cells when HER2 is artificially overexpressed by transfection and cells get treated as HER2 positive cells. Therefore, triple negative breast cancer cell lines were stably transfected with HER2. These cells will be treated with anti-HER2 agents. Molecular analyses will demonstrate whether transfection with HER2 will yield a HER2 positive breast cancer phenotype in that all downstream signaling mechanisms act similarly to a priori HER2 positive cells. Results: Preliminary experiments suggest that proliferation of breast cancer cells transfected with HER2 does not change significantly. Treatment with HER2-specifically blocking antibody trastuzumab leads to significant decrease of proliferation in HER2 transfected, initially triple negative MDA-MB-231 breast cancer cells. Only a moderate decrease in proliferation was observed when lapatinib, a small molecule directed against both EGFR and HER2, was used in both MDA-MB-231 wildtype and HER2-transfected cell lines. Additional results will be presented. Conclusion: We surmise that firstly, transdifferentiation of cancer might become a clinical tool to treat cancer of poor prognosis and secondly that our results might shed light on future therapeutic approaches e.g. small molecule compound screening for endogenous HER2 reactivation / overexpression and subsequent targeted treatment of cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1198. doi:1538-7445.AM2012-1198