Specificities of Lung Adenocarcinoma in Women Who Have Never Smoked

Introduction: No clear data are available on the high rate of tobacco-independent lung cancer in women. We hypothesize that genetic events or hormonal factors may be partly involved. Methods: We aimed to compare clinical, pathological, and biological characteristics of lung cancer in two cohorts of women: smokers and never-smokers. A total of 140 women (63 never-smokers and 77 former/current smokers) with adenocarcinoma, were included in this study. Results: The never-smokers were characterized by a higher age (67 versus 58.7 years; p < 0.0001) and a higher frequency of lepidic features (60.3% versus 37.7%; p = 0.008) compared with smokers. We observed differential genetic alteration repartition in women according to their tobacco status: 50.8% of never-smokers displayed an epidermal growth factor receptor (EGFR) mutation versus 10.4% of smokers (p < 0.001). In contrast, K-Ras was more frequently mutated in smokers (33.8%) than in never-smokers (9.5%; p = 0.001). We also observed a higher percentage of estrogen receptors (ER) expression (p = 0.03; and p = 0.008 with two different antibodies) in patients who never smoked when compared with smokers. There was no significant difference in ER and progesterone receptors between the groups. Finally, ER expression was correlated with the presence of an EGFR mutation. Conclusions: This study suggests that when lung cancer occurs in women who have never smoked, it is more frequently associated with an EGFR mutation and ER expression, with a correlation between both markers. These findings underline the possibility of treating women who have never smoked by targeting both hormonal factors and genetic abnormalities.