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.

Keywords: androgen receptor; early breast cancer; immunohistochemistry; progesterone receptor negative; relapse-free survival.

Figure 1.

Representative histologic images showing immunohistochemical expression of androgen receptor in breast cancer tissue (upper image: androgen receptor expression ⩽5%; lower image: androgen receptor expression ⩾90%) (original magnification, ×100).

Figure 2.

Kaplan−Meier curve showing the relationship between androgen receptor expression and probability of relapse (A) and between androgen receptor expression and probability of survival (B). The numbers in each table describe the number of patients at risk by stratum at different time points. The shaded areas represent the 95% confidence interval of each curve. p-values were generated by the Log-rank test. AR, androgen receptor.

Figure 3.

Scatterplot describing the correlation between estrogen receptor (ER) and androgen receptor (AR) expression. The quantile regression line is represented in red.