4.7 Article

BRAF Mutation Predicts for Poor Outcomes After Metastasectomy in Patients With Metastatic Colorectal Cancer

Journal

CANCER
Volume 120, Issue 15, Pages 2316-2324

Publisher

WILEY-BLACKWELL
DOI: 10.1002/cncr.28729

Keywords

BRAF; colorectal cancer; liver resection; PIK3CA (phosphatidylinositol-4, 5-bisphosphate 3-kinase, catalytic subunit alpha); prognosis

Categories

Funding

  1. American Association for Cancer Research-Colorectal Cancer Coalition Fellows Grant
  2. American Cancer Society Postdoctoral Fellowship
  3. Anbinder Fund

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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. (C) 2014 American Cancer Society.

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