Role of androgen receptor expression in early stage ER+/PgR−/HER2– breast cancer

Abstract

Background: Progesterone receptor (PgR) negative breast cancer (BC) is an aggressive subtype with poor prognosis and reduced response to endocrine treatments. Several studies have suggested that androgen receptor (AR) expression is associated with a favorable tumor biology, longer recurrence free survival (RFS), and overall survival. In the literature no data exist regarding the role of AR expression in early stage estrogen receptor (ER)+/PgR– BCs. The aim of this study was to evaluate the prognostic role of AR expression in this setting. Patients and methods: This is a monocentric retrospective study in which 208 patients who underwent surgical intervention for ER+/PgR−/Human Epidermal growth factor Receptor 2 (HER2)– BC were included. The primary objective was to analyze the relationship between AR expression and RFS. Results: At a median follow-up of 77 months, 75 patients (36%) had a disease relapse (all sites included). AR expression was significantly higher in patients who did not relapse compared with those who relapsed with an impact on RFS (hazard ratio [HR] = 0.99, p = 0.025). Patients with AR expression ⩾80% had a lower risk of relapse compared with those with AR <80% (HR = 0.53, p = 0.008). In addition, breast tumors with higher AR expression had good biological features (low ki67 and nuclear grade) compared with BCs with lower AR expression, at least partly explaining the different outcome. Conclusions: The results of this study support the potential prognostic role of AR in patients with ER+/PgR− BCs and may contribute to the identification of subgroups of high-risk patients.

Intrinsic Subtypes and Androgen Receptor Gene Expression in Primary Breast Cancer. A Meta-Analysis

“…Furthermore, high AR mRNA levels were also maintained in PgR+ patients and even in a subgroup of ER+/PgR+ BC cases compared to the ER+/PgR− subgroup. These results are in agreement with those reported by Tagliaferri et al, who have indicated that low AR levels in cases with ER+/PgR− BCs may contribute to the identification of subgroups of high-risk patients [ 47 ]. In general, our results suggest that a global increase in AR gene expression seems to be a hallmark of HR+ BC.…”

Lost but Not Least—Novel Insights into Progesterone Receptor Loss in Estrogen Receptor-Positive Breast Cancer

“…Conversely, when PgR is lost, another receptor, ERβ, down-regulates ERα target genes, whereas AR enhances ERα target gene transcription and potentially contributes to tumor growth [111]. However, high AR expression is associated with prolonged relapsefree survival, lower grade, and lower number of affected lymph nodes in ERα(+)/PgR(−) BC, thus the mechanistic role of AR and its influence on ERα(+)/PgR(−) tumor aggressiveness requires further studies [112,113]. The loss of nuclear PgR expression does not imply loss of progestin responsiveness in BC cells [114].…”

The Role of Immunohistochemistry in the Workup of Malignant Neoplasms of Unknown Primary Origin at Khartoum Oncology Hospital

“…Some valuable organ-specific markers in CUP workup include ER,GATA3,Mammoglobin A, GCDFP-15 for breast origin.Estrogen Receptor (ER) expression is more among the primary breast cancers than the metastatic cases [4] [12], so it has a limited role in the workup of CUP. ER positivity is identifiedin other malignancies, such as endometrium and ovary carcinomas, thyroid papillary carcinomas, and adnexal tumors of the skin [13][14][15][16].…”