Androgen receptor in advanced breast cancer: is it useful to predict the efficacy of anti-estrogen therapy? (original) (raw)

Evaluation of Androgen Receptor in Relation to Estrogen Receptor (AR/ER) and Progesterone Receptor (AR/PgR): A New Must in Breast Cancer?

Journal of Oncology, 2019

Steroid nuclear receptors are known to be involved in the regulation of epithelial-mesenchymal transition process with important roles in invasion and metastasis initiation. Androgen receptor (AR) has been extensively studied, but its role in relation to breast cancer patient prognosis remains to be clarified. AR/ER ratio has been reported to be an unfavorable prognostic marker in early primary breast cancer, but its role in the patients with advanced disease has to be cleared. We retrospectively analyzed ER, PgR, and AR expression on a case series of 159 specimens of primary BC samples by using immunohistochemistry and 89 patients of these had luminal tumors for which AR and ER expression and survival data were available. For twenty-four patients both primary and metastatic tumors were available. A significantly shorter overall survival was observed in primary tumors with AR/PgR ratio ≥ 1.54 (HR = 2.27; 95% CI 1.30-3.97; p = 0.004). Similarly OS was significantly shorter when ER/Pg...

Combined Androgen and Estrogen Receptor Status in Breast Cancer: Treatment Prediction and Prognosis in a Population-based Prospective Cohort

Clinical cancer research : an official journal of the American Association for Cancer Research, 2015

To evaluate whether tumor androgen receptor (AR) expression was prognostic and/or predictive for endocrine treatment alone or in combination with estrogen receptor (ER). The AR has been hypothesized to have differential prognostic roles in breast cancer depending on tumor ER-status, and to influence endocrine treatment response. A population-based prospective cohort of 1026 patients diagnosed with primary invasive breast cancer in Lund, Sweden between 2002 and 2012 was followed until June 2014. Associations between immunohistochemical AR expression in tumor tissue microarrays, patient and tumor characteristics, and AR genotypes were analyzed. Disease-free survival (DFS) by AR status, and combined ER/AR status was assessed in various treatment groups. AR expression was assessable in 913 tumors. AR+ tumors (85.0%) were associated with higher age (P=0.036) and favorable tumor characteristics. The AR+ status was a prognostic marker for DFS (LogRank P=0.025). There was an interaction bet...

Androgen receptor (AR) expression in 400 breast carcinomas: is routine AR assessment justified?

American Journal of Cancer Research, 2014

Triple negative breast carcinomas (TNBC) do not benefit from hormonal or Herceptin therapies. In search of novel therapeutic targets for TNBC, interest is escalating in a subset of these tumors that are androgen receptor (AR) positive with potential benefit from anti-androgen therapy. Against this background, the frequency of AR expression alone and in combination with other markers and morphologic features was assessed to identify TNBC subtypes for targeted therapy. 400 consecutive invasive mammary carcinomas with known estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR) and HER2 status were selected for study. The frequency of AR positivity alone or in combination with other markers was recorded with specific attention to the morphology of AR+ TNBCs. Ki67 was evaluated in selected group of cases. ASCO/CAP guidelines were used for interpretation of the various biomarkers. Of the 400 tumors, 32 (8%) carcinomas were quadruple negative (ER-, PR-, AR-, Her2-), wh...

Androgen receptor status is highly conserved during tumor progression of breast cancer

Background: With the advent of new and more efficient anti-androgen drugs targeting androgen receptor (AR) in breast cancer (BC) is becoming an increasingly important area of investigation. This would potentially be most useful in triple negative BC (TNBC), where better therapies are still needed. The assessment of AR status is generally performed on the primary tumor even if the tumor has already metastasized. Very little is known regarding discrepancies of AR status during tumor progression. To determine the prevalence of AR positivity, with emphasis on TNBCs, and to investigate AR status during tumor progression, we evaluated a large series of primary BCs and matching metastases and recurrences.

Androgen Receptor Expression in Locally Advanced Breast Cancer Predicts Lack of Pathological Complete Response After Neoadjuvant Treatment

2017

Background: Data regarding the prognostic value of androgen receptor (AR) expression in locally advanced breast cancer (LABC) is limited. We aimed to determine the pathological complete response, defined as ypT0/is and ypN0, in a group of patients with AR-positive breast cancer after preoperative treatment. Methods: We evaluated immunohistochemical AR expression in 40 patients treated in our referral center. Univariate and multivariate models were used to assess the association between AR expression and pathological complete response (pCR). Results: AR expression varied from 75% in estrogen receptor-positive tumors to 11.7% in triple-negative tumors (P < 0.001). Three patients with AR-positive tumors achieved pCR. In the univariate model, AR expression was significantly associated with the absence of pCR (OR = 0.18; 95% CI, 0.04–0.75; P = 0.023). After adjusting for intrinsic breast cancer subtypes, AR-positive tumors had less probability of achieving a pCR compared with AR-negat...

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

Breast cancer research and treatment, 2016

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...