Androgen Receptor Expression Shows Distinctive Significance in ER Positive and Negative Breast Cancers

Tsang, Julia Y. S.; Ni, Yun‐Bi; Chan, Siu‐Ki; Shao, Mumin; Law, Ben M. F.; Tan, Puay Hoon; Tse, Gary M.

doi:10.1245/s10434-014-3629-2

Cited by 67 publications

(61 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…28 AR AR is a steroid nuclear receptor and is expressed more frequently than ER in breast cancer. 63 Although the precise role of AR in breast carcinogenesis is not clear, the possibility of it serving as a therapeutic target, especially in TNBC, is of significant interest. 35 Clinically, AR positivity is associated with better prognosis and, more recently, 21 associated with a lower recurrence score using the 21-gene test.…”

Section: Ck5/6mentioning

confidence: 99%

Immunohistochemical Surrogates for Molecular Classification of Breast Carcinoma: A 2015 Update

Tang¹,

Tse

2016

Archives of Pathology &Amp; Laboratory Medicine

Self Cite

131

109

View full text Add to dashboard Cite

Context.-The pioneering works on molecular classification (MC) by Perou and Sorlie et al in the early 2000s using global gene expression profiling identified 5 intrinsic subtypes of invasive breast cancers (IBCs): luminal A, luminal B, normal breast-like, HER2-enriched, and basallike subtypes, each unique in incidence, survival, and response to therapy. Because the application of gene expression profiling in daily practice is not economical or practical at the present time, many investigators have studied the use of immunohistochemical (IHC) surrogates as a substitute for determining the MC of IBC.Objective.-To discuss the continuing efforts that have been made to develop clinically significant and readily available IHC surrogates for the MC of IBC.Data Sources.-Data were obtained from pertinent peer-reviewed English-language literature.Conclusions.-The most commonly used IHC surrogates are estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2), dividing IBC into luminal, HER2, and triple-negative subtypes. The addition of Ki-67, cytokeratin 5, and epidermal growth factor receptor (EGFR) separates luminal B from luminal A subtypes, and basal-like subtype from triple-negative breast cancer. More recently, biomarkers such as androgen receptor and p53 have been shown to further stratify these molecular subtypes. Although many studies of IHC-based MC have shown clinical significance similar to gene expression profiling-defined MC, its critical limitations are: (1) a lack of standardization in terminology, (2) a lack of standardization in biomarkers used for each subtype, and (3) the lack of a uniform cutoff for each biomarker. A panel of IHC surrogates for each subtype of IBC is proposed.

show abstract

Section: Ck5/6mentioning

confidence: 99%

Immunohistochemical Surrogates for Molecular Classification of Breast Carcinoma: A 2015 Update

Tang¹,

Tse

2016

Archives of Pathology &Amp; Laboratory Medicine

Self Cite

131

109

View full text Add to dashboard Cite

show abstract

“…The vast majority of ERa-and PR-positive breast cancers also express AR (Ogawa et al 2008, Park et al 2011, Alshenawy 2012, Secreto et al 2012, Santagata et al 2014, Sultana et al 2014, Tsang et al 2014, and AR expression is observed in up to 50% of ERa-and/or PR-negative breast cancers (Gucalp et al (2013), Tsang et al (2014); reviewed in Hickey et al (2012), McNamara et al (2013) and Nahleh (2008)), making AR an attractive target for the treatment of multiple types of breast cancer. However, it is currently unclear how to stratify individual breast cancers based on whether they will respond favourably to androgen treatment or not.…”

Section: Ar Expression In Mammary Epitheliummentioning

confidence: 99%

“…This is somewhat remarkable, particularly with respect to the breast, as it has long been known that androgen hormones inhibit pubertal and post-pubertal breast growth, and that treatment with androgen can cause regression of breast tumours (Lamar & Rezek 1958, Thomas et al 1962, Tormey et al 1983, Forsbach et al 2000, Rose et al 2000. Indeed, AR is the most frequently expressed sex steroid receptor in both primary and secondary (metastatic) breast cancers, making it a highly prevalent therapeutic target (McNamara et al 2013, Santagata et al 2014, Tsang et al 2014. We have recently reviewed the role of AR signalling in normal and malignant breast tissues (Hickey et al 2012), and McNamara et al (2013) provide an update on that theme in this issue including a section on intracrine androgen metabolism in the breast and the implication of this for AR signalling in breast cancer.…”

Section: Introductionmentioning

confidence: 99%

Bringing androgens up a NOTCH in breast cancer

Tarulli

Butler

Tilley

et al. 2014

Endocrine-Related Cancer

View full text Add to dashboard Cite

While it has been known for decades that androgen hormones influence normal breast development and breast carcinogenesis, the underlying mechanisms have only been recently elucidated. To date, most studies have focused on androgen action in breast cancer cell lines, yet these studies represent artificial systems that often do not faithfully replicate/ recapitulate the cellular, molecular and hormonal environments of breast tumours in vivo. It is critical to have a better understanding of how androgens act in the normal mammary gland as well as in in vivo systems that maintain a relevant tumour microenvironment to gain insights into the role of androgens in the modulation of breast cancer development. This in turn will facilitate application of androgen-modulation therapy in breast cancer. This is particularly relevant as current clinical trials focus on inhibiting androgen action as breast cancer therapy but, depending on the steroid receptor profile of the tumour, certain individuals may be better served by selectively stimulating androgen action. Androgen receptor (AR) protein is primarily expressed by the hormone-sensing compartment of normal breast epithelium, commonly referred to as oestrogen receptor alpha (ERa (ESR1))-positive breast epithelial cells, which also express progesterone receptors (PRs) and prolactin receptors and exert powerful developmental influences on adjacent breast epithelial cells. Recent lineage-tracing studies, particularly those focussed on NOTCH signalling, and genetic analysis of cancer risk in the normal breast highlight how signalling via the hormone-sensing compartment can influence normal breast development and breast cancer susceptibility. This provides an impetus to focus on the relationship between androgens, AR and NOTCH signalling and the crosstalk between ERa and PR signalling in the hormone-sensing component of breast epithelium in order to unravel the mechanisms behind the ability of androgens to modulate breast cancer initiation and growth.

show abstract

“…Immunohistochemical studies have demonstrated that AR expression varies between the different subtypes, with a higher positivity in luminal A-like tumours and a lower positivity in TNBCs (Luo et al 2010, Park et al 2010, Loibl et al 2011, Tsang et al 2014. 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.…”

Section: Ar As a Prognostic Factormentioning

confidence: 99%

“…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

View full text Add to dashboard Cite

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.

show abstract

Androgen Receptor Expression Shows Distinctive Significance in ER Positive and Negative Breast Cancers

Abstract: AR expression was different in ER+ and ER- cancers and had different clinical implications. AR alone may not be a good marker for MA subtype. Its expression in MA may have substantial prognostic implication and as such warrants further validation.

Cited by 67 publications

References 37 publications

Immunohistochemical Surrogates for Molecular Classification of Breast Carcinoma: A 2015 Update

Immunohistochemical Surrogates for Molecular Classification of Breast Carcinoma: A 2015 Update

Bringing androgens up a NOTCH in breast cancer

Revising the role of the androgen receptor in breast cancer

Contact Info

Product

Resources

About