Cytoplasmic ERβ1 expression is associated with survival of patients with Stage IV lung adenocarcinoma and an EGFR mutation at exon 21 L858R subsequent to treatment with EGFR-TKIs

The present study assessed whether estrogen receptor (ER)β1 is associated with the survival of patients with advanced lung adenocarcinoma, with or without mutations of the epidermal growth factor receptor (EGFR) following treatment with EGFR-tyrosine kinase inhibitors (TKIs). Pathologically confirmed stage IV lung adenocarcinomas were assessed for EGFR mutations and ERβ1 expression. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and the log-rank test. A total of 122 out of the 201 (60.7%) patients had EGFR mutations, 64 (31.8%) of which were EGFR Del19 and 58 mutations (28.9%) were EGFR exon 21 L858R mutation. The presence of EGFR mutations was significantly increased in female patients compared with male patients (P<0.001) and in non-smokers compared with smokers (P<0.001). Patients with EGFR mutations had a significantly improved PFS and OS compared with patients without EGFR mutations treated with EGFR-TKIs. Furthermore, ERβ1 expression was significantly increased in patients with EGFR mutations compared with patients without EGFR mutations (P=0.001). However, the median PFS (P=0.005) and OS (P=0.002) of patients carrying the EGFR exon 21 L858R mutation was significantly decreased in patients with tumors where ERβ1 cytoplasmic expression was high. The multivariate analysis demonstrated that ERβ1 expression was the only independent predictor of PFS (P=0.002) and OS (P=0.003) in patients carrying the EGFR exon 21 L858R mutation. The data demonstrated that ERβ1 expression may predict outcomes of patients with lung adenocarcinoma treated with EGFR-TKI.