Premium
BRAF mutation predicts for poor outcomes after metastasectomy in patients with metastatic colorectal cancer
Author(s) -
Yaeger Rona,
Cercek Andrea,
Chou Joanne F.,
Sylvester Brooke E.,
Kemeny Nancy E.,
Hechtman Jaclyn F.,
Ladanyi Marc,
Rosen Neal,
Weiser Martin R.,
Capanu Marinela,
Solit David B.,
D'Angelica Michael I.,
Vakiani Efsevia,
Saltz Leonard B.
Publication year - 2014
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.28729
Subject(s) - medicine , metastasectomy , kras , colorectal cancer , oncology , stage (stratigraphy) , cancer , paleontology , biology
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. Cancer 2014;120:2316–2324. © 2014 American Cancer Society .