Somatic Profile in Lung Cancers Is Associated to Reproductive Factors in Never-Smokers Women: Results from the IFCT-1002 BioCAST study

ABSTRACT Background: Lung cancer in women is on the rise, with a higher proportion occurring in lifelong never-smokers. Lung cancer in never-smokers (LCINS) exhibits a high frequency of driver oncogene alterations. In this study, we aimed to investigate whether exposure to reproductive factors in women with LCINS may modulate the molecular pattern. Methods: All newly diagnosed LCINSs were included in a prospective, observational study (IFCT-1002 BioCAST). Each patient responded to a questionnaire including reproductive factors. Biomarker test results were also collected. Results: 260 women were included in this analysis, and 166 alterations were characterized. EGFR mutation frequency proved greater among patients with late menarche (74% in age >14 vs. 40% and 41% for 12-14 and ≤12 years, respectively; p=0.020) and tended to decrease with increasingly late age at menopause. In multivariate analysis, EGFR mutation frequency increased by 23% per increment of 1 year of age at menarche (p=0.048), and by 9% for each year at age at first birth (p=0.035). ALK alteration frequency was greater in women with high parity (50% in ≥5 vs. 12% and 7% for 1-4 and nulliparity, respectively; p=0.021). Conclusion: In a cohort of women LCINSs, female hormonal factors appear to impact molecular pattern.