Prognostic relevance of androgen receptor detection in operable breast cancer

Søiland, Håvard; Kørner, Hartwig; Skaland, Ivar; Janssen, Emiel A. M.; Gudlaugsson, Einar; Varhaug, Jan Erik; Baak, J. P. A.; Søreide, Jon Arne

doi:10.1002/jso.21156

Cited by 21 publications

(17 citation statements)

References 42 publications

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“…In the former, a strong better prognostication was conferred by AR positivity among patients with ER þ breast cancer both in univariate and multivariate analysis, which is in line with previously published studies (8,9,11,41,42,53). Preclinical evidence suggesting an AR-ER cross-talk also support these findings, indicating that AR can antagonize ER signaling depending on the relative levels of these two steroid receptors (2).…”

Section: Discussionsupporting

confidence: 87%

The Prognostic Role of Androgen Receptor in Patients with Early-Stage Breast Cancer: A Meta-analysis of Clinical and Gene Expression Data

Božović-Spasojević

Zardavas

Brohée

et al. 2017

Clinical Cancer Research

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Purpose: Androgen receptor (AR) expression has been observed in about 70% of patients with breast cancer, but its prognostic role remains uncertain.Experimental Design: To assess the prognostic role of AR expression in early-stage breast cancer, we performed a metaanalysis of studies that evaluated the impact of AR at the protein and gene expression level on disease-free survival (DFS) and/or overall survival (OS). Eligible studies were identified by systematic review of electronic databases using the MeSH-terms "breast neoplasm" and "androgen receptor" and were selected after a qualitative assessment based on the REMARK criteria. A pooled gene expression analysis of 35 publicly available microarray data sets was also performed from patients with early-stage breast cancer with available gene expression and clinical outcome data.Results: Twenty-two of 33 eligible studies for the clinical meta-analysis, including 10,004 patients, were considered as evaluable for the current study after the qualitative assessment. AR positivity defined by IHC was associated with improved DFS in all patients with breast cancer [multivariate (M) analysis, HR 0.46; 95% confidence interval (CI) 0.37-0.58, P < 0.001] and better OS [M-HR 0.53; 95% CI, 0.38-0.73, P < 0.001]. Thirty-five datasets including 7,220 patients were eligible for the pooled gene expression analysis. High AR mRNA levels were found to confer positive prognosis overall in terms of DFS (HR 0.82; 95% CI 0.72-0.92;P ¼ 0.0007) and OS (HR 0.84; 95% CI, 0.75-0.94; P ¼ 0.02) only in univariate analysis.Conclusions: Our analysis, conducted among more than 17,000 women with early-stage breast cancer included in clinical and gene expression analysis, demonstrates that AR positivity is associated with favorable clinical outcome. Clin Cancer Res; 23(11); 2702-12. Ó2016 AACR.

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Section: Discussionsupporting

confidence: 87%

The Prognostic Role of Androgen Receptor in Patients with Early-Stage Breast Cancer: A Meta-analysis of Clinical and Gene Expression Data

Božović-Spasojević

Zardavas

Brohée

et al. 2017

Clinical Cancer Research

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“…The majority of studies investigating the relationship between AR levels in the primary tumour, clinical characteristics and disease outcome have found that AR expression is a favourable prognostic indicator (reviewed by Hickey et al (2012)). In cohorts not selected on the basis of estrogen receptor-a (ERa (ESR1)) status, AR positivity has been associated with longer relapse-free, metastasis-free and overall survival, smaller tumour size and lower histological grade (Bryan et al 1984, Langer et al 1990, Kuenen-Boumeester et al 1992, Soreide et al 1992, Schippinger et al 2006, Agrawal et al 2008, Gonzalez et al 2008, Hanley et al 2008, Ogawa et al 2008, Soiland et al 2008, Park et al 2010, Yu et al 2011, Peters et al 2012, Honma et al 2013. High AR levels have also been associated with a favourable response to chemotherapy and hormonal therapy, including antioestrogens, aromatase inhibitors and progestins (Teulings et al 1980, Bryan et al 1984, Birrell et al 1995, Agrawal et al 2008, Chintamani et al 2010, Chanplakorn et al 2011, Loibl et al 2011.…”

Section: Prognostic Value Of Ar Expression In Breast Cancermentioning

confidence: 99%

“…High AR levels have also been associated with a favourable response to chemotherapy and hormonal therapy, including antioestrogens, aromatase inhibitors and progestins (Teulings et al 1980, Bryan et al 1984, Birrell et al 1995, Agrawal et al 2008, Chintamani et al 2010, Chanplakorn et al 2011, Loibl et al 2011. Importantly, AR has also been shown to be an independent predictor of relapse-free, metastasis-free and/or overall survival in some studies (Soreide et al 1992, Gonzalez et al 2008, Soiland et al 2008, Yu et al 2011. However, other studies have shown that AR levels do not predict the response to endocrine therapy or relapse-free or overall survival (Allegra et al 1979, Soreide et al 1992, Carreno et al 2007.…”

Section: Prognostic Value Of Ar Expression In Breast Cancermentioning

confidence: 99%

Complexities of androgen receptor signalling in breast cancer

McNamara¹,

Moore²,

Hickey³

et al. 2014

Endocrine-Related Cancer

123

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While the clinical benefit of androgen-based therapeutics in breast cancer has been known since the 1940s, we have only recently begun to fully understand the mechanisms of androgen action in breast cancer. Androgen signalling pathways can have either beneficial or deleterious effects in breast cancer depending on the breast cancer subtype and intracellular context. This review discusses our current knowledge of androgen signalling in breast cancer, including the relationship between serum androgens and breast cancer risk, the prognostic significance of androgen receptor (AR) expression in different breast cancer subtypes and the downstream molecular pathways mediating androgen action in breast cancer cells. Intracrine androgen metabolism has also been discussed and proposed as a potential mechanism that may explain some of the reported differences regarding dichotomous androgen actions in breast cancers. A better understanding of AR signalling in this disease is critical given the current resurgence in interest in utilising contemporary AR-directed therapies for breast cancer and the need for biomarkers that will accurately predict clinical response.

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“…A number of studies have investigated the prognostic potential of AR expression in BCs, with the majority finding the AR to be associated with favourable clinicopathological features. In ERa-positive BCs, AR has been found to correlate with lower grade, reduced lymph node involvement and longer disease-free survival, and this correlation is proportional to the levels of AR expression (Schippinger et al 2006, Søiland et al 2008, Castellano et al 2010, Hu et al 2011, Park et al 2011, Tsang et al 2014. In one study, AR and ERa levels were analysed in 1467 BC tumours from postmenopausal women enrolled in the Nurses' Health Study (Hu et al 2011).…”

Section: Ar As a Prognostic Factormentioning

confidence: 99%

Revising the role of the androgen receptor in breast cancer

Fioretti¹,

Sita‐Lumsden²,

Bevan³

et al. 2014

Journal of Molecular Endocrinology

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Breast cancer (BC) is traditionally viewed as an oestrogen-dependent disease in which the androgen receptor (AR) is inhibitory, counteracting the oncogenic activity of oestrogen receptor a (ERa (ESR1)). Most probably as a result of this crosstalk, the AR has prognostic value in ER-positive disease, with AR positivity reported to correlate with a better prognosis. Activation of the AR pathway has been previously used as a therapeutic strategy to treat BC, but its usage declined following the introduction of the anti-oestrogen tamoxifen. More recently, it has been demonstrated that a subset of triple-negative BCs (molecular apocrine) are dependent upon androgen signalling for growth and therapies that inhibit androgen signalling, currently used for the treatment of prostate cancer, e.g. the antiandrogen bicalutamide and the CYP17 inhibitor abiraterone acetate are undergoing clinical trials to investigate their efficacy in this BC subtype. This review summarises the current knowledge of AR activity in BC.

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Prognostic relevance of androgen receptor detection in operable breast cancer

Abstract: Methods that can detect AR localized in the cytoplasm yield important prognostic information, and further studies in patients with operable breast cancer are warranted.

Cited by 21 publications

References 42 publications

The Prognostic Role of Androgen Receptor in Patients with Early-Stage Breast Cancer: A Meta-analysis of Clinical and Gene Expression Data

The Prognostic Role of Androgen Receptor in Patients with Early-Stage Breast Cancer: A Meta-analysis of Clinical and Gene Expression Data

Complexities of androgen receptor signalling in breast cancer

Revising the role of the androgen receptor in breast cancer

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