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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) &agr; 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&bgr; and progesterone receptors between the groups. Finally, ER&agr; 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&agr; 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.