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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