title: Specificities of lung adenocarcinoma in women who have never smoked.
abstract: BACKGROUND
  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) α 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 ERβ and progesterone receptors between the groups. Finally, ERα 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 ERα 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.
authors.affiliation: Unité d'Oncologie Thoracique, Service de Pneumologie, Hôpital Larrey-CHU de Toulouse, Université de Toulouse III (Paul Sabatier), Cedex 9, France. mazieres.j@chu-toulouse.fr
authors.forename: Julien
authors.initials: J
authors.lastname: Mazières
authors.forename: Isabelle
authors.initials: I
authors.lastname: Rouquette
authors.forename: Benoit
authors.initials: B
authors.lastname: Lepage
authors.forename: Julie
authors.initials: J
authors.lastname: Milia
authors.forename: Laurent
authors.initials: L
authors.lastname: Brouchet
authors.forename: Nicolas
authors.initials: N
authors.lastname: Guibert
authors.forename: Michèle
authors.initials: M
authors.lastname: Beau-Faller
authors.forename: Pierre
authors.initials: P
authors.lastname: Validire
authors.forename: Paul
authors.initials: P
authors.lastname: Hofman
authors.forename: Pierre
authors.initials: P
authors.lastname: Fouret
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015331:Cohort Studies; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism; D012907:Smoking; D018631:ras Proteins / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins