Expression of androgen receptor in breast cancer and its significance as a prognostic factor

Yu, Qi; Niu, Yun; Liu, N.; Zhang, J.Z.; Liu, T.J.; Zhang, R.J.; Wang, S.L.; Ding, Xiumin; Xiao, Xu-qi

doi:10.1093/annonc/mdq586

Cited by 111 publications

(130 citation statements)

References 31 publications

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“…Several studies have also suggested that the androgen receptor might be a good predictor of survival in patients with breast cancer. 30,31,33 In this study, 5-year disease-free survival in androgen receptor-positive patients was better than that in androgen receptor-negative patients, but the difference did not achieve statistical significance in univariate survival analysis.…”

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confidence: 67%

“…24,[28][29][30][31][32][33][34] Therefore, the androgen receptor is potentially an important molecule in the clinical care of breast cancer. In this study, androgen receptor positivity rates were significantly different in the subtype groups, ranging from 76.3% in the HHR group to 14.8% in the NHR-LTH2 group, indicating that the androgen receptor plays different roles in these different subtypes and necessitates diverse androgen receptor-targeted therapy.…”

mentioning

confidence: 99%

“…In this study, androgen receptor positivity rates were significantly different in the subtype groups, ranging from 76.3% in the HHR group to 14.8% in the NHR-LTH2 group, indicating that the androgen receptor plays different roles in these different subtypes and necessitates diverse androgen receptor-targeted therapy. [28][29][30][31][32][33][34] For example, androgen receptor signaling might be one of the major mechanisms involved in stimulating the action of hormone receptors, or vice versa. Androgen receptor-targeted therapy in addition to endocrine therapy might be a sensible approach for this group.…”

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confidence: 99%

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Subtype classification for prediction of prognosis of breast cancer from a biomarker panel: correlations and indications

Chen¹,

Yuan²,

Wen³

et al. 2014

IJN

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Background Hormone receptors, including the estrogen receptor and progesterone receptor, human epidermal growth factor receptor 2 (HER2), and other biomarkers like Ki67, epidermal growth factor receptor (EGFR, also known as HER1), the androgen receptor, and p53, are key molecules in breast cancer. This study evaluated the relationship between HER2 and hormone receptors and explored the additional prognostic value of Ki67, EGFR, the androgen receptor, and p53. Methods Quantitative determination of HER2 and EGFR was performed in 240 invasive breast cancer tissue microarray specimens using quantum dot (QD)-based nanotechnology. We identified two subtypes of HER2, ie, high total HER2 load (HTH2) and low total HER2 load (LTH2), and three subtypes of hormone receptor, ie, high hormone receptor (HHR), low hormone receptor (LHR), and no hormone receptor (NHR). Therefore, breast cancer patients could be divided into five subtypes according to HER2 and hormone receptor status. Ki67, p53, and the androgen receptor were determined by traditional immunohistochemistry techniques. The relationship between hormone receptors and HER2 was investigated and the additional value of Ki67, EGFR, the androgen receptor, and p53 for prediction of 5-year disease-free survival was assessed. Results In all patients, quantitative determination showed a statistically significant ( P <0.001) negative correlation between HER2 and the hormone receptors and a significant positive correlation ( P <0.001) between the estrogen receptor and the progesterone receptor ( r =0.588), but a significant negative correlation ( P <0.001, r =−0.618) with the HHR subtype. There were significant differences between the estrogen receptor, progesterone receptor, and HER2 subtypes with regard to total HER2 load and hormone receptor subtypes. The rates of androgen receptor and p53 positivity were 46.3% and 57.0%, respectively. Other than the androgen receptor, differences in expression of Ki67, EGFR, and p53 did not achieve statistical significance ( P >0.05) between the five subtypes. EGFR and Ki67 had prognostic significance for 5-year disease-free survival in univariate analysis, but the androgen receptor and p53 did not. Multivariate analysis identified that EGFR expression had predictive significance for 5-year disease-free survival in hormone-receptor positive patients and in those with the lymph node-positive breast cancer subtype. Conclusion Hormone receptor expression was indeed one of the molecular profiles in the subtypes identified by quantitative HER2 and vice versa. EGFR status may provide discriminative prognostic information in addition to HER2 and hormone receptor status, and should be integrated into routine practice to help formulate more specific prediction of the prognosis and appropr...

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Subtype classification for prediction of prognosis of breast cancer from a biomarker panel: correlations and indications

Chen¹,

Yuan²,

Wen³

et al. 2014

IJN

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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

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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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Androgen Receptor Function and Androgen Receptor–Targeted Therapies in Breast Cancer

et al. 2017

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Androgen receptor-targeted treatments for breast cancer are in development and have shown promising preliminary results. In-depth understanding of AR and AR-related signaling pathways would improve the treatment strategies for AR-positive breast cancer. Further preclinical and clinical studies of AR-targeted drugs alone and in combination with other drugs are justified and warranted to clarify the biology of AR and inform the development of AR-targeted therapies to improve survival outcome in patients with breast cancer.

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Expression of androgen receptor in breast cancer and its significance as a prognostic factor

Abstract: Our data suggest that AR may provide another specific definition of breast cancer subtypes and reveal a potential role in DCIS progression. These findings may help develop new therapies.

Cited by 111 publications

References 31 publications

Subtype classification for prediction of prognosis of breast cancer from a biomarker panel: correlations and indications

Subtype classification for prediction of prognosis of breast cancer from a biomarker panel: correlations and indications

Complexities of androgen receptor signalling in breast cancer

Androgen Receptor Function and Androgen Receptor–Targeted Therapies in Breast Cancer

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