Abstract Disparities in breast cancer (BC) stage of presentation and survival are well documented in patients of different ethnicities. These differences are undoubtedly due to a combination of extrinsic and intrinsic factors. Our group is focused on the genetic contributions to these disparities. Recent observations by our group and others suggest not only the involvement of specific genes contributing to BC risk in African-American (AA) women, but that multiple distinct ethnic-specific gene expression patterns exist in both matched cancerous and normal breast tissue samples. We report the first results of a parallel study which is addressing an unanswered question: are there ethnic-specific differences in the transcriptome of normal breast tissue? We are completing gene expression profiling studies in normal breast FFPE samples from 25 AA and 25 Caucasian (Cauc) women with no history of breast cancer. Laser capture micro-dissection (LCM) is used to further identify and extract epithelial vs stromal cells from each FFPE slide for use in RNA expression profiling. RNA isolation and hybridization occurs in collaboration with Almac Diagnostics (Dx) using their proprietary Breast Cancer DSA array. Gene expression data analyses involves multiple statistical packages developed for DNA microarray studies, and is focusing on comparison of gene expression profiles across four study groups- AA vs Cauc samples and epithelial vs stroma cells. For baseline comparison, a subset of this study group (10 AA and 10 Cauc samples non-LCM dissected) has also been analyzed. Results from these non-LCM dissected samples displayed expression differences between AA and Cauc in 333 known genes. Applying the stringency criteria of a fold change of two or greater and a statistical p-value of 0.01, reduced the significant gene list to 61 genes. Initial pathway analyses indicate these genes are involved in cell adhesion, G-protein signaling, apoptosis and survival pathways, and cytoskeleton remodeling - all critical pathways for cell survival. These initial results are being validated in the LCM-dissected samples, and our latest results will be presented. Results from analyses of these normal samples will be compared to our previous results obtained in matched tumor-normal triple negative AA and Cauc breast cancer samples (as well as publicly available data sets). Combined analysis of tumor and normal breast expression (transcriptome) data will help to better understand the possible significance of gene expression differences in breast tissue between ethnic groups. 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 4196. doi:1538-7445.AM2012-4196