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

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Title: Prognostic significance of androgen receptor expression in invasive breast cancer: transcriptomic and protein expression analysis
Authors: Aleskandarany, MA
Abduljabbar, R
Ashankyty, I
Elmouna, A
Jerjees, D
Ali, S
Buluwela, L
Diez-Rodriguez, M
Caldas, C
Green, AR
Ellis, IO
Rakha, EA
Item Type: Journal Article
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.
Issue Date: 11-Aug-2016
Date of Acceptance: 1-Aug-2016
URI: http://hdl.handle.net/10044/1/55287
DOI: 10.1007/s10549-016-3934-5
ISSN: 1573-7217
Publisher: Springer Verlag
Start Page: 215
End Page: 227
Journal / Book Title: Breast Cancer Research and Treatment
Volume: 159
Issue: 2
Copyright Statement: The final publication is available at Springer via http://dx.doi.org/10.1007/s10549-016-3934-5
Sponsor/Funder: Cancer Research UK
Funder's Grant Number: C37/A12011
Keywords: Science & Technology
Life Sciences & Biomedicine
Oncology
Breast cancer
Androgen receptor
METABRIC
Molecular
Clinical
Outcome
PROGESTERONE-RECEPTORS
IN-SITU
ESTROGEN
CARCINOMA
FLUOXYMESTERONE
PROLIFERATION
TAMOXIFEN
SUBTYPES
THERAPY
TISSUES
1112 Oncology And Carcinogenesis
Oncology & Carcinogenesis
Publication Status: Published
Appears in Collections:Division of Surgery
Division of Cancer
Faculty of Medicine



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