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

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

Authors

Mohammad A. Aleskandarany

Rezvan Abduljabbar

Ibraheem Ashankyty

Ahmed Elmouna

Dena Jerjees

Simak Ali

Laki Buluwela

Maria Diez-Rodriguez

Carlos Caldas

EMAD RAKHA Emad.Rakha@nottingham.ac.uk
Professor of Breast Cancer Pathology



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 less than 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 less than 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 less than 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.

Journal Article Type Article
Publication Date Sep 30, 2016
Journal Breast Cancer Research and Treatment
Print ISSN 0167-6806
Electronic ISSN 1573-7217
Publisher BMC
Peer Reviewed Peer Reviewed
Volume 159
Issue 2
Pages 215-227
APA6 Citation Aleskandarany, M. A., Abduljabbar, R., Ashankyty, I., Elmouna, A., Jerjees, D., Ali, S., …Rakha, E. A. (2016). Prognostic significance of androgen receptor expression in invasive breast cancer: transcriptomic and protein expression analysis. Breast Cancer Research and Treatment, 159(2), 215-227. doi:10.1007/s10549-016-3934-5
DOI https://doi.org/10.1007/s10549-016-3934-5
Publisher URL https://link.springer.com/article/10.1007%2Fs10549-016-3934-5
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