title: Incidence of EGFR exon 19 deletions and L858R in tumor specimens from men and cigarette smokers with lung adenocarcinomas.
abstract: OBJECTIVE
  EGFR mutations underlie the sensitivity of lung cancers to erlotinib and gefitinib and can occur in any patient with this illness. Here we examine the frequency of EGFR mutations in smokers and men.
  
  
  METHODS
  We determined the frequency of EGFR mutations and characterized their association with cigarette smoking status and male sex.
  
  
  RESULTS
  We tested 2,142 lung adenocarcinoma specimens for the presence of EGFR exon 19 deletions and L858R. EGFR mutations were found in 15% of tumors from former smokers (181 of 1,218; 95% CI, 13% to 17%), 6% from current smokers (20 of 344; 95% CI, 4% to 9%), and 52% from never smokers (302 of 580; 95% CI, 48% to 56%; P < .001 for ever v never smokers). EGFR mutations in former or current smokers represented 40% of all those detected (201 of 503; 95% CI, 36% to 44%). EGFR mutations were found in 19% (157 of 827; 95% CI, 16% to 22%) of tumors from men and 26% (346 of 1,315; 95% CI, 24% to 29%) of tumors from women (P < .001). EGFR mutations in men represented 31% (157 of 503; 95% CI, 27% to 35%) of all those detected.
  
  
  CONCLUSIONS
  A large number of EGFR mutations are found in adenocarcinoma tumor specimens from men and people who smoked cigarettes. If only women who were never smokers were tested, 57% of all EGFR mutations would be missed. Testing for EGFR mutations should be considered for all patients with adenocarcinoma of the lung at diagnosis, regardless of clinical characteristics. This strategy can extend the use of EGFR tyrosine kinase inhibitors to the greatest number individuals with the potential for substantial benefit.
authors.affiliation: Memorial Sloan-Kettering Cancer Center and Weill Medical College of Cornell University, New York, NY 10065, USA.
authors.forename: Sandra P
authors.initials: SP
authors.lastname: D'Angelo
authors.forename: M Catherine
authors.initials: MC
authors.lastname: Pietanza
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Johnson
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Riely
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Miller
authors.forename: Camelia S
authors.initials: CS
authors.lastname: Sima
authors.forename: Maureen F
authors.initials: MF
authors.lastname: Zakowski
authors.forename: Valerie W
authors.initials: VW
authors.lastname: Rusch
authors.forename: Marc
authors.initials: M
authors.lastname: Ladanyi
authors.forename: Mark G
authors.initials: MG
authors.lastname: Kris
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology / Q000235:genetics; D000077192:Adenocarcinoma of Lung; D066246:ErbB Receptors / Q000235:genetics*; D005091:Exons; D005260:Female; D006801:Humans; D015994:Incidence; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics; D008297:Male; D017384:Sequence Deletion; D012907:Smoking / Q000235:genetics*
chemical_list: D066246:ErbB Receptors