Abstract B067: Taxonomy of breast cancer based on normal cell phenotype and ontology

The classification of lymphoma and leukemia is successfully done by using normal cell types as a reference point which is one of the many reasons that better therapies are available for their treatment. In case of breast cancer, clinically it is classified as Estrogen Receptor positive, Human Epidermal Growth Factor Receptor 2 (Her2) positive and triple negative breast cancer while in the research settings, it has been classified by mRNA expression profiling but these classification systems are still evolving. Our laboratory attempted to classify breast cancer by examining the expression of different keratin isoforms and Hormone Receptors (HR) studied through immunostaining in 36 normal breast samples and later in 1731 breast tumors from the Nurses9 Health Study (NHS) cohort with a patient follow up extending beyond 25 years. Among the various receptors tested, three of these receptors: Androgen Receptor, Estrogen Receptor and Vitamin D Receptor were capable of identifying four major subgroups being designated as HR0-3, depending on the number of hormone receptors present. More importantly, radically different survival outcomes were observed between these HR sub-groups through Kaplan Meier curve analysis; which highlights their usefulness as vital biological markers as wells as targets for breast cancer treatment. Furthermore, the characterization of these HR was carried out in 20 different breast cancer cell lines and the combination of different receptor modulators alone or in combination was attempted with better anti-proliferative effects being observed in the combinatorial group than either treatment alone. Thus, our new classification not only re-classifies breast cancer but also gives insight on how patients could be treated through targeting hormone receptors. Citation Format: Ankita Thakkar, Sandro Santagata, Ayse Ergonul, Bin Wang, Terri Woo, Rong Hu, J. Chuck Harrell, George McNamara, Matthew Schwede, Aedin C. Culhane, David Kindelberger, Scott Rodig, Andrea Richardson, Stuart J. Schnitt, Rulla M. Tamimi, Tan A. Ince. Taxonomy of breast cancer based on normal cell phenotype and ontology. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research: Genetics, Biology, and Clinical Applications; Oct 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2013;11(10 Suppl):Abstract nr B067.