Abstract LB-224: Development of a novel breast cancer segregation panel assay for multiple genetic subtyping based on gene expression modules developed from Oncomine™

Abstract

Abstract Breast cancer is a highly heterogeneous disease as evidenced by comprehensive genetic studies which have revealed multiple subtypes using gene expression profiling and cell lineage classifier analyses. Previous studies have characterized different subtypes including normal breast-like, luminal epithelial A, luminal epithelial B, Her 2 over-expression and basal type carcinoma. However, the genetic variation within breast cancer is far more diverse than these core subtypes, and it is necessary to fully characterize this diversity in order to move beyond simple prognosis and to specifically predict drug sensitivity. In a review of global gene expression and SNP-based cytogenetic data of more than 5,000 breast cancer patients in the Oncomine™ database, we have been able to characterize approximately 30 different genetic variations that are shared by 1% or more of the breast cancer population. These core, independent variables reflect diverse elements of the disease at a molecular level including cell lineage, dysregulated core biological functions, factors of cell growth, and importantly, the tumor microenvironment. Further genetic subtypes are characterized within the various large and focal genomic amplifications, such as Her2 and Myc, as well as focal expression events present subpopulations of patients. In aggregate these genetic variables represent all of the major genetic factors that present within breast cancer. Currently biomarker/diagnostic approaches have tended to be over-tailored to specific clinical questions and therefore have lacked broad applicability, with every diagnostic test requiring a custom gene set and tailored signature and in some cases, requiring separate validated assays using multiple technologies and consequent splitting of clinical samples. To overcome these limitations, we have developed a single, 96-gene qRT-PCR test for rapid breast cancer companion diagnostics development using FFPE tumor tissue. All 30 of the core variables or “modules” are represented by this test which reports on both gene expression and chromosomal amplification events. We demonstrate in this study that this single test, with its multiple modules, can report on standard histopathological parameters, such as ER, PR and Her2, and reproduce existing prognostic and predictive genomic signatures. Data will be presented on prediction of overall survival, neoadjuvant chemotherapy response, and in-vitro sensitivity to MEK and PI3K inhibitors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-224. doi:10.1158/1538-7445.AM2011-LB-224