Abstract

<div>Abstract<p><b>Purpose:</b> Previously, we found that gene expression in histologically normal breast epithelium (NlEpi) from women at high breast cancer risk can resemble gene expression in NlEpi from cancer-containing breasts. Therefore, we hypothesized that gene expression characteristic of a cancer subtype might be seen in NlEpi of breasts containing that subtype.</p><p><b>Experimental Design:</b> We examined gene expression in 46 cases of microdissected NlEpi from untreated women undergoing breast cancer surgery. From 30 age-matched cases [15 estrogen receptor (ER)+, 15 ER−] we used Affymetryix U133A arrays. From 16 independent cases (9 ER+, 7 ER−), we validated selected genes using quantitative real-time PCR (qPCR). We then compared gene expression between NlEpi and invasive breast cancer using four publicly available data sets.</p><p><b>Results:</b> We identified 198 genes that are differentially expressed between NlEpi from breasts with ER+ (NlEpiER+) compared with ER− cancers (NlEpiER−). These include genes characteristic of ER+ and ER− cancers (e.g., <i>ESR1</i>, <i>GATA</i>3, and <i>CX3CL1</i>, <i>FABP7</i>). qPCR validated the microarray results in both the 30 original cases and the 16 independent cases. Gene expression in NlEpiER+ and NlEpiER− resembled gene expression in ER+ and ER− cancers, respectively: 25% to 53% of the genes or probes examined in four external data sets overlapped between NlEpi and the corresponding cancer subtype.</p><p><b>Conclusions:</b> Gene expression differs in NlEpi of breasts containing ER+ compared with ER− breast cancers. These differences echo differences in ER+ and ER− invasive cancers. NlEpi gene expression may help elucidate subtype-specific risk signatures, identify early genomic events in cancer development, and locate targets for prevention and therapy. <i>Clin Cancer Res; 17(2); 236–46. ©2010 AACR</i>.</p></div>

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