The Impact of Estrogen Receptor Expression on Mutational Status in the Evolution of Non-Small Cell Lung Cancer

The impact of ER expression on mutational status was examined in non-small cell lung cancer using a published molecular epidemiology study in Japan. Sample size was 876 cases. ER-positive status was associ-ated with EGFR mutations and a lower frequency of mutations in TP53 and CTNNB1, suggesting that the ER plays a critical role in mutations associated with lung cancer evolution. Background: The role of estrogen receptor (ER) status in the carcinogenesis of lung cancer and its impact on progno-sis remain unclear. Materials and Methods: We previously reported a prospective, multicenter, molecular epidemiol-ogy study (Japan Molecular Epidemiology for Lung Cancer Study [JME]). We examined the relationship of ER status with reproductive and hormonal factors, mutational profile, and survival using JME study data. Patients were enrolled between July 2012 and December 2013, with follow-up until November, 2017. Results: Among 441 ever-and 435 never -smokers, ER expression was observed in 46.4% and 53.5%, respectively ( P = .022). Hormone use and reproductive history of female patients were not associated with ER status. Mutations in EGFR ( P = .003), TP53 ( P = .007), and CTNNB1 ( P = .027) were significantly associated with ER expression. Multivariate analysis showed that mutations in EGFR ( P = .032) and CTNNB1 ( P = .026) were significantly associated with ER expression, whereas TP53 mutations exhibited a trend toward significance ( P = .059). Relapse-free survival (RFS) was longer in all the patients with ER -positive tumors than those with ER-negative tumors ( P = .021). RFS and overall survival were longer ( P = .024, P = .011, respectively) in the stage I patients with ER-positive tumors than those with ER-negative tumors. Conclusion: ER beta expression is positively associated with EGFR mutations and negatively with TP53 and CTNNB1 mutations. ER-positive tumors can be associated with better prognosis of the patients, suggesting that ER expression with coexisting EGFR mutations and wild-type TP53 contribute to the biology of non-small cell lung cancer.