title: BRAF mutation predicts for poor outcomes after metastasectomy in patients with metastatic colorectal cancer.
abstract: BACKGROUND
  BRAF mutations occur in 5% to 11% of patients with metastatic colorectal cancer (mCRC) and have been associated with poor prognosis. The current study was undertaken to determine the clinicopathologic characteristics, PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha) mutation frequency, and outcomes after metastasectomy in patients with BRAF-mutant mCRC.
  
  
  METHODS
  Data from 1941 consecutive patients with mCRC who underwent KRAS/BRAF mutation testing between 2009 and 2012 at a single institution were identified to identify BRAF-mutant mCRC cases (92 cases). BRAF wild-type mCRC cases from 2011 (423 cases) served as a control group.
  
  
  RESULTS
  BRAF-mutated mCRC was found to be significantly associated with older age at diagnosis, female sex, right-sided location, poorly differentiated morphology, and mucinous histology compared with wild-type cases. BRAF-mutant cases more frequently progressed from stage III disease (32% vs 17%; P = .003) and among those patients with stage III disease, T4 disease was more common (48% vs 27%; P = .05). PIK3CA was found to be co-mutated in 5% of BRAF-mutant tumors versus 17% of KRAS-mutant tumors (P < .01) and 4% of BRAF/KRAS wild-type cases. Patients with BRAF-mutated mCRC presented more frequently with peritoneal involvement (26% vs 14%; P < 0.01) and less frequently with liver-limited metastases (41% vs 63%; P < .01). Patients with BRAF-mutated mCRC were less likely to undergo metastasectomy (41% vs 26% at 2 years from diagnosis of metastatic disease; P < .01) and were found to have lower overall survival (P < .01) after metastasectomy.
  
  
  CONCLUSIONS
  BRAF-mutant mCRC is associated with worse clinical outcome. Patients with BRAF-mutant tumors more commonly develop peritoneal metastases, less frequently present with disease limited to the liver, and have shorter survival after metastasectomy compared with patients with BRAF wild-type tumors.
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors.forename: Rona
authors.initials: R
authors.lastname: Yaeger
authors.forename: Andrea
authors.initials: A
authors.lastname: Cercek
authors.forename: Joanne F
authors.initials: JF
authors.lastname: Chou
authors.forename: Brooke E
authors.initials: BE
authors.lastname: Sylvester
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Kemeny
authors.forename: Jaclyn F
authors.initials: JF
authors.lastname: Hechtman
authors.forename: Marc
authors.initials: M
authors.lastname: Ladanyi
authors.forename: Neal
authors.initials: N
authors.lastname: Rosen
authors.forename: Martin R
authors.initials: MR
authors.lastname: Weiser
authors.forename: Marinela
authors.initials: M
authors.lastname: Capanu
authors.forename: David B
authors.initials: DB
authors.lastname: Solit
authors.forename: Michael I
authors.initials: MI
authors.lastname: D'Angelica
authors.forename: Efsevia
authors.initials: E
authors.lastname: Vakiani
authors.forename: Leonard B
authors.initials: LB
authors.lastname: Saltz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058534:Class I Phosphatidylinositol 3-Kinases; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000601:surgery*; D005260:Female; D006801:Humans; D008297:Male; D059146:Metastasectomy; D008875:Middle Aged; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics* / Q000378:metabolism; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: 5-bisphosphate 3-kinase; BRAF; PIK3CA (phosphatidylinositol-4; catalytic subunit alpha); colorectal cancer; liver resection; prognosis
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