Abstract

In breast cancer (BC), androgen receptor (AR) expression is related to estrogen receptor (ER) and/or progesterone receptor (PgR) expression. AR expression is an indicator of good prognosis in breast cancer regardless of hormone receptor (HR) status. In this study, we evaluated the effect of AR-related gene expression on clinical characterization of metastatic BC. We performed RNA-Seq to evaluate gene expression using mRNA extracted from 37 patients with metastatic BC. Intrinsic subtype prediction, analysis of differential gene expression, and gene set enrichment pathway analysis were then performed. Metastatic BCs were categorized into three subgroups based on AR, ER, PgR, and HER2 expression. According to this subcategorization, 70 genes including AR, ER, and HER2 were differentially expressed among the three groups. In gene set enrichment pathway analysis, the low AR group was associated with the cell cycle pathway, whereas mammalian target of rapamycin (mTOR) pathways was prevalent in the high ER and AR group. In survival analysis, a higher level of AR expression correlated with prolonged overall survival in metastatic BC (high expression vs. low expression, median OS 53.1 vs. 27.2 months, p=.001). In conclusion, we propose that AR and AR-related gene expression could be utilized to predict the prognosis of metastatic BC and thus may be useful in treatment planning for refractory BC.

Highlights

  • Breast cancer (BC) consists of heterogeneous subtypes distinguished by different gene expression patterns [1]

  • androgen receptor (AR) expression was dependent on estrogen receptor (ER)/progesterone receptor (PgR) and HER2 expression, our research suggests that AR expression has an additional role as a prognostic marker of metastatic breast cancer (BC)

  • The impact of AR expression seemed to override conventional BC subtypes based on ER, PgR, and HER2 expression upon subcategorization

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Summary

Introduction

Breast cancer (BC) consists of heterogeneous subtypes distinguished by different gene expression patterns [1]. BC is usually classified into three subtypes according to estrogen receptor (ER)/progesterone receptor (PgR) expression and HER2 overexpression [4] using immunohistochemistry (IHC). These three IHC molecular markers are used as reliable predictive and prognostic indicators for treatment planning in BC patients [5]. Hormone receptor (HR)-positive BC, which expresses ER and/or PgR, is sensitive to anti-estrogen treatment [6] and HER2 overexpression is a predictive marker of HER2-targeted treatment in HER2-positive breast cancer [7]. Triple-negative breast cancer (TNBC), BC without ER/PgR expression or HER2 overexpression, has heterogeneous histologic characteristics, no identified therapeutic target molecules [8], and a dismal prognosis [9]

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