title: Clinical characteristics and course of 63 patients with BRAF mutant lung cancers.
abstract: BACKGROUND
  Mutant BRAF is a driver oncogene found in 2% of lung adenocarcinomas and represents a target for therapy. We examined the clinical characteristics and course of patients with lung adenocarcinomas harboring BRAF mutations.
  
  
  METHODS
  We identified patients with lung adenocarcinomas harboring BRAF mutations between 2009 and 2013 detected using a mass spectrometry-based polymerase chain reaction genotyping assay of hot-spot mutations involving codons corresponding to amino acids V600, D594, and G469 of BRAF. Patient characteristics and treatment outcomes were analyzed. Overall survival (OS) was compared with stage-matched patients with KRAS and EGFR mutant lung adenocarcinomas.
  
  
  RESULTS
  Sixty-three patients were diagnosed with BRAF mutant lung adenocarcinomas between 2009 and 2013 (V600, 36; non-V600, 27). The majority of patients with BRAF mutations were smokers (92%), although patients with V600 mutations were more likely to be light/never-smokers compared with patients with non-V600 mutations (42% versus 11%; p = 0.007). Of the 32 patients with early-stage disease, six (19%; 95% confidence interval 7%-36%) developed second primary lung cancers harboring KRAS mutations. Patients with advanced V600 mutant lung adenocarcinomas had a better survival from diagnosis compared with those with non-V600 mutant lung adenocarcinomas (3-year OS: 24% versus 0%; p < 0.001).
  
  
  CONCLUSIONS
  This is the largest series of patients with BRAF mutant lung cancers described. Most patients were heavy smokers. Nineteen percent of patients with early-stage BRAF mutant lung cancers developed second primary lung cancers harboring KRAS mutations. Patients with advanced lung adenocarcinomas harboring V600 mutations have an improved OS compared with those with non-V600 mutations.
authors.affiliation: Departments of *Medicine, Thoracic Oncology Service, Division of Solid Tumor Oncology, †Epidemiology and Biostatistics, and ‡Pathology, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY.
authors.forename: Anya M
authors.initials: AM
authors.lastname: Litvak
authors.forename: Paul K
authors.initials: PK
authors.lastname: Paik
authors.forename: Kaitlin M
authors.initials: KM
authors.lastname: Woo
authors.forename: Camelia S
authors.initials: CS
authors.lastname: Sima
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Hellmann
authors.forename: Maria E
authors.initials: ME
authors.lastname: Arcila
authors.forename: Marc
authors.initials: M
authors.lastname: Ladanyi
authors.forename: Charles M
authors.initials: CM
authors.lastname: Rudin
authors.forename: Mark G
authors.initials: MG
authors.lastname: Kris
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Riely
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf