Gender disparities in hormone positive lung cancer.

Abstract

e21552 Background: Lung cancer has not declined in U.S. women as much as it has in men over the past 20 years despite similar rates of smoking cessation among the genders. We explored whether differences in hormone receptor status could contribute to the reason for the observation. Methods: A total of 3,256 non-small lung cancer (NSCLC) tumor samples submitted for molecular profiling between 2013-2018 were retrospectively identified for having hormone receptor (HR) expression results. HR-positive (HR+) status was defined as ≥ 1+ and 1% nuclear staining of Estrogen Receptor alpha (SP1, Ventana) and/or Progesterone Receptor (IE2, Ventana) by immunohistochemistry. DNA sequencing by NGS included cases sequenced by the Illumina MiSeq hot spot 47 gene panel (n = 2753) and Illumina NextSeq 592 gene panel (n = 503). Tumor mutation burden (TMB) was measured by counting somatic non- synonymous missense mutations on the 592 gene panel and ≥ 10 mutations/Megabase (mut/Mb) was considered high. Fisher’s Exact, Chi- square and likelihood ratio (LR) tests were utilized for statistical analyses. Results: Hormone receptor positivity (HR+) was identified in 318 women and 186 men, 504/3256 or 15% of NSCLC. EGFR mutation subtypes observed were Exon19del (46%), L858R (28%), uncommon non-classical (17%), G719X|S768I|L861Q (5%). HR+ occurred more commonly in women compared to men (20% vs 11%, p < 0.001). HR+ NSCLC had the same age distribution as HR-negative (HR-) cancers (range: 16-94 and 18-93, respectively). Compared to patients (pts) who were HR-, pts with HR+ NSCLC were more likely to harbor activating EGFR mutations in men and women (LR 1.39, p = 0.0017), and less likely to have mutations in TP53 (LR 0.83, p = 0.0076), K-RAS (LR 0.66, p < 0.0001), or translocations in ALK (LR 0.46 p = 0.0190). No differences in the incidence of ERBB2 or BRAF mutations were identified. The median tumor mutational burden was equivalent in HR+ vs. HR- pts, both 9 mut/MB. Conclusions: The disparity in the prevalence of hormone receptors in lung cancers affecting men and women deserves further exploration. The presence of hormone receptors in NSCLC is increased in women and in tumors bearing EGFR mutations. Further elucidation of the mechanism and dual targeting of EGFR and ER in patients with HR+ NSCLC deserves exploration.