Estrogen receptor subtypes and survival outcomes in non-small cell lung cancer

Abstract

Aim: Estrogen receptors (ERs), ERα and ERβ, are frequently detected in lung cancers, yet their prognostic impact on non-small cell lung cancer (NSCLC) outcomes remains uncertain. This study aims to assess the pooled prevalence and prognostic significance of ERα and ERβ in NSCLC, with a focus on gender differences.

Methods: We performed a systematic review and meta-analysis, identifying studies from major databases, including PubMed, Cochrane Library, and Embase, that reported ERα and ERβ expression and survival outcomes in NSCLC. Hazard ratios (HRs) with 95 % confidence intervals (CIs) were calculated using random-effects models to assess associations with overall survival (OS). Heterogeneity was evaluated using the I² statistic, and publication bias was examined with funnel plots. Statistical analyses were conducted in R (version 4.3.0) utilizing the 'meta' package."

Results: Eighteen studies comprising 3842 patients met the inclusion criteria. ERα positivity was observed in 32 % of cases, whereas ERβ positivity was found in 60 %. ERα positivity in males was 53 %, and in females was 47 %. Meanwhile, ERβ positivity was seen in 49 % of males and 51 % of females. The pooled HR for ERα was 1.17 (95 % CI: 0.60-2.27), indicating no significant association with OS. However, ERβ positivity was linked to a statistically significant reduction in mortality risk (HR 0.85, 95 % CI: 0.72-0.99, p = 0.04). Subgroup analysis demonstrated a higher mortality hazard in males compared to females (HR 1.42, 95 % CI: 1.22-1.67, p < 0.005).

Conclusion: NSCLC exhibits high rates of ERβ expression, which is linked to improved survival outcomes. In contrast, ERα expression is less prevalent, and its prognostic significance remains uncertain. These findings underscore ERβ as a promising therapeutic target in NSCLC, emphasizing the need for continued research into hormone-targeted treatments in lung cancer, especially given that approximately 50 % of both male and female patients with NSCLC express ERβ.

Keywords: Analysis; Estrogen receptor; Immunohistochemistry; Non-small cell lung cancer; Survival.