Expression and Clinical Significance of Androgen Receptor in Triple-Negative Breast Cancer

Asano, Yuka; Kashiwagi, Shinichiro; Goto, Wataru; Tanaka, Sayaka; Morisaki, Tamami; Takashima, Tsutomu; Noda, Shinichi; Onoda, Naoyoshi; Ohsawa, Masahiko; Hirakawa, Kosei; Ohira, Masaichi

doi:10.3390/cancers9010004

Cited by 61 publications

(61 citation statements)

References 38 publications

(65 reference statements)

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“…Furthermore, we reported that the rate of pCR to NAC was 24.1% for TNBC AR+ group compared with 60% of QNBC group. These findings matched with voluminous previous reports (Hilborn et al, 2016;Gerratana et al, 2018;Masuda et al, 2013;Asano et al, 2016;Asano et al, 2017, andovanović et al, 2017).…”

Section: Discussionsupporting

confidence: 92%

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Neoadjuvant Chemotherapy in Triple Negative Breast Cancer: Correlation between Androgen Receptor Expression and Pathological Response

Mohammed

Elsayed

Algazar

et al. 2020

Asian Pac J Cancer Prev

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Triple-negative breast cancer (TNBC) is a heterogeneous disease on the pathological, molecular, and clinical levels. It represents approximately 17% of all breast cancers (BCs) and have aggressive behavior compared to other molecular subtypes. QNBC is TNBC that lacks the expression of androgen receptor (AR), Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) and accounts for 63%-87% of TNBC with more aggressive behavior than the other molecular subtypes (

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Section: Discussionsupporting

confidence: 92%

“…The results were comparable; the pCR in TNBC AR+ was less frequent than in QNBC. Similarly, Masuda et al through a retrospective study on 146 patients with TNBC, reported lower pCR in TNBC AR+ compared with QNBC (Asano et al, 2017).…”

Section: Discussionmentioning

confidence: 76%

Neoadjuvant Chemotherapy in Triple Negative Breast Cancer: Correlation between Androgen Receptor Expression and Pathological Response

Mohammed

Elsayed

Algazar

et al. 2020

Asian Pac J Cancer Prev

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“…It has been reported that AR is expressed in 60–70% of ER − BC and in approximately 68% of the cases in this research . The AR signalling pathway has a significant role in the proliferation and survival of ER − BCs, and inhibition of AR has a therapeutic value in in‐vitro and in‐vivo models of ER − AR + BC cells .…”

Section: Discussionsupporting

confidence: 50%

Clinical significance of PDEF factor expression and its relation to androgen receptor in ER⁻ breast cancer

Cao

et al. 2018

Histopathology

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Aims The mechanism of androgen receptor (AR) promoting tumour growth in oestrogen receptor‐negative (ER−) breast cancer (BC) is undetermined. Prostate‐derived ETS factor (PDEF) is highly restricted to the hormone‐regulated tissues of epithelial cells, such as those in the prostate, breast and other tissues. It has been demonstrated that PDEF expression is associated with AR in prostate cancer. In this research, we aimed to investigate the relationship between PDEF and AR in ER− BC. Methods and results We immunohistochemically evaluated the correlation between PDEF and AR expression in 246 cases of ER− invasive BC, and investigated their relationship in ER− BC cell lines. The expression of PDEF was associated with the positive expression of AR (P < 0.001) and a worse survival rate (P = 0.006). PDEF+ tumours were significantly more often AR+ (P < 0.001). AR and PDEF were more often co‐expressed and the series of AR+PDEF+ (126 of 246, 51.2%) had a poor survival rate (P = 0.046). In Cox models, PDEF expression (P = 0.028) was an independent predictor for overall survival (OS). At the cellular protein and mRNA levels, our experiments also showed a statistically significant positive correlation between PDEF and AR, and that PDEF may be regulated by AR. Conclusions PDEF is associated with markers of bad prognosis, supporting its role as a growth promoter in ER− BC. Our findings also provide evidence that PDEF is strongly correlated with AR expression in ER− breast cancer; it may be a downstream target gene of AR and a potential prognostic factor in ER− BC.

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“…Several studies have shown that AR expression in luminal tumours (ER+) is associated with lower tumour grade, smaller tumour size, lower proliferative index (Ki67 level) and more importantly, AR expression in ER+ tumours is an independent prognostic factor of a good outcome (Castellano et al 2010, Niemeier et al 2010, Aleskandarany et al 2016, Bozovic-Spasojevic et al 2016). On the other hand, up to 31% of ER-negative (ER−) BCs are reported to be AR+ (Niemeier et al 2010, Park et al 2010, but the prognostic impact of AR expression in this subset of BCs is not clear (Luo et al 2010, Hu et al 2011, Park et al 2011, Pistelli et al 2014, Vera-Badillo et al 2014, Hilborn et al 2016, Jiang et al 2016, Asano et al 2017.…”

Section: Introductionmentioning

confidence: 99%

The role of the AR/ER ratio in ER-positive breast cancer patients

Rangel¹,

Rondón-Lagos²,

Annaratone³

et al. 2018

Endocrine-Related Cancer

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The significance of androgen receptor (AR) in breast cancer (BC) management is not fully defined, and it is still ambiguous how the level of AR expression influences oestrogen receptor-positive (ER+) tumours. The aim of the present study was to analyse the prognostic impact of AR/ER ratio, evaluated by immunohistochemistry (IHC), correlating this value with clinical, pathological and molecular characteristics. We retrospectively selected a cohort of 402 ER+BC patients. On each tumour, IHC analyses for AR, ER, PgR, HER2 and Ki67 were performed and AR+ cases were used to calculate the AR/ER value. A cut-off of ≥2 was selected using receiver-operating characteristic (ROC) curve analyses. RNA from 19 cases with AR/ER≥2 was extracted and used for Prosigna-PAM50 assays. Tumours with AR/ER≥2 (6%) showed more frequent metastatic lymph nodes, larger size, higher histological grade and lower PgR levels than cases with AR/ER<2. Multivariate analysis confirmed that patients with AR/ER≥2 had worse disease-free interval (DFI) and disease-specific survival (DSS) (hazard ratios (HR) = 4.96 for DFI and HR = 8.69 for DSS, both ≤ 0.004). According to the Prosigna-PAM50 assay, 63% (12/19) of these cases resulted in intermediate or high risk of recurrence categories. Additionally, although all samples were positive for ER assessed by IHC, the molecular test assigned 47.4% (9/19) of BCs to intrinsic non-luminal subtypes. In conclusion, the AR/ER ratio ≥2 identifies a subgroup of patients with aggressive biological features and may represent an additional independent marker of worse BC prognosis. Moreover, the Prosigna-PAM50 results indicate that a significant number of cases with AR/ER≥2 could be non-luminal tumours.

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Expression and Clinical Significance of Androgen Receptor in Triple-Negative Breast Cancer

Cited by 61 publications

References 38 publications

Neoadjuvant Chemotherapy in Triple Negative Breast Cancer: Correlation between Androgen Receptor Expression and Pathological Response

Neoadjuvant Chemotherapy in Triple Negative Breast Cancer: Correlation between Androgen Receptor Expression and Pathological Response

Clinical significance of PDEF factor expression and its relation to androgen receptor in ER⁻ breast cancer

The role of the AR/ER ratio in ER-positive breast cancer patients

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Expression and Clinical Significance of Androgen Receptor in Triple-Negative Breast Cancer

Cited by 61 publications

References 38 publications

Neoadjuvant Chemotherapy in Triple Negative Breast Cancer: Correlation between Androgen Receptor Expression and Pathological Response

Neoadjuvant Chemotherapy in Triple Negative Breast Cancer: Correlation between Androgen Receptor Expression and Pathological Response

Clinical significance of PDEF factor expression and its relation to androgen receptor in ER− breast cancer

The role of the AR/ER ratio in ER-positive breast cancer patients

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Clinical significance of PDEF factor expression and its relation to androgen receptor in ER⁻ breast cancer