BRAF mutation predicts for poor outcomes after metastasectomy in patients with metastatic colorectal cancer Journal Article


Authors: Yaeger, R.; Cercek, A.; Chou, J. F.; Sylvester, B. E.; Kemeny, N. E.; Hechtman, J. F.; Ladanyi, M.; Rosen, N.; Weiser, M. R.; Capanu, M.; Solit, D. B.; D'Angelica, M. I.; Vakiani, E.; Saltz, L. B.
Article 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. © 2014 American Cancer Society.
Keywords: adult; controlled study; human tissue; aged; gene mutation; major clinical study; overall survival; cancer staging; colorectal cancer; cytoreductive surgery; gene; tumor localization; lung lobectomy; ovariectomy; tumor differentiation; mutational analysis; age; liver metastasis; lung metastasis; liver resection; sex difference; ovary metastasis; oncogene k ras; peritoneum metastasis; b raf kinase; braf; braf gene; recurrence free survival; metastatic colorectal cancer; wedge resection; metastasis resection; cancer prognosis; prognosis; human; male; female; priority journal; article; 5-bisphosphate 3-kinase; catalytic subunit alpha); pik3ca (phosphatidylinositol-4; phosphatidylinositol 4,5 bisphosphate 3 kinase catalytic subunit alpha gene
Journal Title: Cancer
Volume: 120
Issue: 15
ISSN: 0008-543X
Publisher: Wiley Blackwell  
Date Published: 2014-08-01
Start Page: 2316
End Page: 2324
Language: English
DOI: 10.1002/cncr.28729
PROVIDER: scopus
PUBMED: 24737664
PMCID: PMC4928876
DOI/URL:
Notes: Export Date: 2 September 2014 -- CODEN: CANCA -- Source: Scopus
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MSK Authors
  1. Joanne Fu-Lou Chou
    153 Chou
  2. Leonard B Saltz
    578 Saltz
  3. Neal Rosen
    356 Rosen
  4. David Solit
    431 Solit
  5. Marinela Capanu
    205 Capanu
  6. Marc Ladanyi
    861 Ladanyi
  7. Martin R Weiser
    337 Weiser
  8. Rona Denit Yaeger
    64 Yaeger
  9. Efsevia Vakiani
    162 Vakiani
  10. Nancy Kemeny
    345 Kemeny