Prognostic role of Amphiregulin and the correlation with androgen receptor in invasive breast cancer

Abstract

Background: In androgen-sensitive prostate cancer, androgenic stimulation induces the synthesis of amphiregulin (AREG). Research is lacking on the role of AREG in invasive breast cancer and the co-expression with androgen receptor (AR) status.

Materials and methods: The present study investigated the prognostic role of AREG in invasive breast cancer cases (N = 298) and the co-expression with the AR status as analysed by immunohistochemistry (IHC).

Results: The samples were divided into groups according to AREG expression levels: low/no expression (AREG^low/no) and high expression (AREG^high). As shown by cytoplasmic immunostaining, 46.0% (137/298) of invasive breast cancers were AREG^high, and 54.0% (161/298) of cases were AREG^low/no. Co-expression of the AR and AREG accounted for 62.4% (186/298) of cases. A Kaplan-Meier analysis revealed that AREG^high and AR⁺/AREG^high decreased patients' overall survival (OS) (P = 0.002 and P = 0.006, respectively) and disease-free survival (DFS) (P < 0.001 and P < 0.001, respectively). In Cox models, AR⁺/AREG^high remained an independent prognostic indicator of OS and DFS in invasive breast cancer (hazard ratio [HR], 0.591, 95% confidence interval [CI], 0.407-0.859, P = 0.006; HR, 0.449, 95% CI, 0.236-0.853, P = 0.014, respectively). AREG^high remained an independent prognostic indicator of OS and DFS in estrogen receptor (ER)-negative tumours (P < 0.05).

Conclusions: This study suggested that AREG and the AR were co-expressed in invasive breast cancer. Thus, AREG and the AR may be valuable prognostic biomarkers in invasive breast cancer and promising therapeutic targets, especially in ER-negative breast cancer.

Keywords: Amphiregulin; Androgen receptor; ER-negative breast cancer; Invasive breast cancer; Prognosis.