title: Erlotinib efficacy in NSCLC patients with high polysomy of chromosome 7 and EGFR/KRas wild-type tumors.
abstract: BACKGROUND
  More than even before, the efficacy of epidermal growth factors (EGFRs) tyrosine kinase inhibitors in non-small-cell lung cancer patients carrying EGFR wild-type tumors has been under investigation. EGFR wild-type patients represent a large and heterogeneous group of patients. In this setting, the role played by high polysomy of chromosome 7 still remains controversial. Indeed, previous reports did not discriminate between chromosome 7 high polysomy and EGFR amplification and/or did not investigate the concurrent presence of EGFR and KRas mutations.
  
  
  METHODS
  We retrospectively collected data from 163 patients analyzed for EGFR status (mutation, amplification, chromosome 7 trysomy, and polysomy), in addition to KRas mutation, between 2000 and 2010 in our institute. Erlotinib was administered to 73 of them. Objective responses and progression-free survivals to erlotinib were evaluated.
  
  
  RESULTS
  High polysomy of chromosome 7 characterized 17% (28 of 163) of EGFR/KRas wild-type tumors, independently of smoking status. In this group, 13 patients received erlotinib at progression. The treatment led one complete and four partial responses, and five stable diseases. Two patients progressed. One patient was lost to follow-up. The mean time to progression was 9 months.
  
  
  CONCLUSIONS
  Among the EGFR wild-type population, when analyzed separately, high polysomy of chromosome 7 was the only molecular feature conferring clear signs of sensitivity to erlotinib. Therefore, the evaluation of high polysomy of chromosome 7 could become a helpful tool to predict for the benefit from epidermal growth factors tyrosine kinase inhibitors in selected cases.
authors.affiliation: *Medical Oncology Department, Thoracic Oncology Division, and †Pathology and Laboratory Medicine Department, Pathology Division, European Institute of Oncology, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Toffalorio
authors.forename: Filippo
authors.initials: F
authors.lastname: de Marinis
authors.forename: Fabio
authors.initials: F
authors.lastname: Conforti
authors.forename: Gianluca
authors.initials: G
authors.lastname: Spitaleri
authors.forename: Chiara
authors.initials: C
authors.lastname: Catania
authors.forename: Cristina
authors.initials: C
authors.lastname: Noberasco
authors.forename: Chiara
authors.initials: C
authors.lastname: Lazzari
authors.forename: Fabio
authors.initials: F
authors.lastname: Vecchio
authors.forename: Viviana
authors.initials: V
authors.lastname: Stufano
authors.forename: Massimo
authors.initials: M
authors.lastname: Barberis
authors.forename: Tommaso
authors.initials: T
authors.lastname: De Pas
mesh_terms: D000782:Aneuploidy; D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002897:Chromosomes, Human, Pair 7; D015331:Cohort Studies; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics*; D000069347:Erlotinib Hydrochloride; D005260:Female; D011905:Genes, ras; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D011799:Quinazolines / Q000627:therapeutic use*; D018631:ras Proteins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins