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Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 2/2016

01-09-2016 | Preclinical study

Prognostic significance of androgen receptor expression in invasive breast cancer: transcriptomic and protein expression analysis

Authors: Mohammad A. Aleskandarany, Rezvan Abduljabbar, Ibraheem Ashankyty, Ahmed Elmouna, Dena Jerjees, Simak Ali, Laki Buluwela, Maria Diez-Rodriguez, Carlos Caldas, Andrew R. Green, Ian O. Ellis, Emad A. Rakha

Published in: Breast Cancer Research and Treatment | Issue 2/2016

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Abstract

Differential prognostic roles of Androgen Receptor (AR) have been proposed in breast cancer (BC) depending on tumour oestrogen receptor (ER) status. This study aimed to evaluate the prognostic and/or predictive significance of AR expression in invasive BC. In this study AR expression was studied on a large (n = 1141) consecutive series of early-stage (I–III) BC using tissue microarray and immunohistochemistry (IHC). AR mRNA expression was assessed in a subset of cases. The prognostic impact of AR mRNA expression was externally validated using the online BC gene expression data sets (n = 25 data sets, 4078 patients). Nuclear AR IHC expression was significantly associated with features of good prognosis including older age, smaller tumour size, lower grade and lobular histology particularly in the ER-positive tumours. AR was associated with ER-related markers GATA3, FOXa1, RERG and BEX1. Negative association was observed with HER2, p53, Ki67, TK1, CD71 and AGTR1. AR Overexpression was associated with longer survival (p < 0.001), independent of tumour size, grade, stage [p = 0.033, hazard ratio (HR) = 0.80 95 % CI = 0.64–0.98]. Similar associations were maintained in ER+ tumours in univariate and multivariate analysis (p < 0.01) both in patients with and without adjuvant endocrine or chemotherapy. AR mRNA expression showed significant association with tumour grade, molecular subtypes, and longer 10 and 15 years survival in luminal BC. In the external validation cohorts, AR gene expression data were associated with improved patients’ outcome (p < 0.001, HR = 0.84, 95 % CI 0.79–0.90). AR is not only an independent prognostic factor in ER-positive luminal BC but is also expressed in ER-negative tumours. AR could act as a molecular target in patients with ER-positive disease predicting response to adjuvant therapy.
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Metadata
Title
Prognostic significance of androgen receptor expression in invasive breast cancer: transcriptomic and protein expression analysis
Authors
Mohammad A. Aleskandarany
Rezvan Abduljabbar
Ibraheem Ashankyty
Ahmed Elmouna
Dena Jerjees
Simak Ali
Laki Buluwela
Maria Diez-Rodriguez
Carlos Caldas
Andrew R. Green
Ian O. Ellis
Emad A. Rakha
Publication date
01-09-2016
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 2/2016
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-016-3934-5

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