Estrogen receptor β and estrogen receptor α36 predict differential outcome of patients with breast cancer

Abstract

Background: Clinical management of breast cancer is guided by assessment of tumor parameters, including histological features and biomarkers. Estrogen receptors alpha (ERα) and beta (ERβ) are involved in the carcinogenesis and progression of breast cancer. Among the ERs, ERα66, the main type of ERα, is one of the most powerful indictors for molecular classification, treatment and prognosis of breast cancer, while the clinical significance of ERβ in breast cancer is elusive. Moreover, ERα36, a variant of ERα66, has recently been identified as an important molecule involved in breast cancer progression, but the clinical relevance of its expression in breast cancer needs to be further clarified. Therefore, this study is aimed to evaluate the prognostic value of ERβ and ERα36 in human breast cancer. Methods: We examined ERβ and ERα36 expression in breast cancer specimens from 124 patients with complete followed-up by immunohistochemistry. To assess the prognostic values, we generated disease-free survival (DFS) curves by Kaplan-Meier method and performed multivariate analysis by Cox proportional hazard regression model. Results: An inverse correlation between ERβ and ERα36 expression was observed (r=−0.196, P=0.029). The expression of ERβ was inversely associated with lymph node metastasis (P=0.007), whereas ERα36 expression was positively correlated with TNM stage (P=0.006) and tumor size (P=0.026). Patients with ERβ-positive exhibited better DFS rate than those with ERβ-negative (P=0.019). Conversely, patients with ERα36-positive exhibited poorer DFS rate than those with ERα36-negative (P=0.047). ERβ-negative/ERα36-positive patients had the poorest DFS rate (P=0.014). Cox regression analysis showed that ERβ was a protective prognostic factor (HR=0.336, P=0.026), and ERα36 was a poor prognostic indicator (HR=2.737, P=0.029). Conclusions: Our results suggest that both ERβ and ERα36 can act as the prognostic indictors and the combination of the two indictors has a better prognostic value for breast cancer.