Predictive and Prognostic Roles of BRAF Mutation in Stage III Colon Cancer: Results from Intergroup Trial CALGB 89803

被引：222

作者：

Ogino, Shuji ^{[1
,2
,3
]}

Shima, Kaori ^{[2
,3
]}

Meyerhardt, Jeffrey A. ^{[2
,3
]}

McCleary, Nadine J. ^{[2
,3
]}

Ng, Kimmie ^{[2
,3
]}

Hollis, Donna ^{[8
]}

Saltz, Leonard B. ^{[9
]}

Mayer, Robert J. ^{[2
,3
]}

Schaefer, Paul ^{[10
]}

Whittom, Renaud ^{[11
]}

Hantel, Alexander ^{[12
]}

Benson, Al B., III ^{[13
]}

Spiegelman, Donna ^{[4
,6
,7
]}

Goldberg, Richard M. ^{[14
]}

Bertagnolli, Monica M. ^{[5
]}

Fuchs, Charles S. ^{[2
,3
,4
]}

机构：

[1] Harvard Univ, Dana Farber Canc Inst, Brigham & Womens Hosp, Ctr Mol Oncol Pathol,Med Sch,Dept Pathol, Boston, MA 02215 USA

[2] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Boston, MA 02215 USA

[4] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA

[5] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA

[6] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA

[7] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA

[8] Duke Univ, Med Ctr, CALGB Stat Ctr, Durham, NC USA

[9] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA

[10] Toledo Community Hosp Oncol Program, NCCTG, Toledo, OH USA

[11] Hop Sacre Coeur, NCIC, Montreal, PQ H4J 1C5, Canada

[12] Loyola Univ, Stritch Sch Med, SWOG, Maywood, IL 60153 USA

[13] Northwestern Univ, Chicago, IL 60611 USA

[14] Univ N Carolina, Chapel Hill, NC USA

来源：

CLINICAL CANCER RESEARCH | 2012年 / 18卷 / 03期

关键词：

ISLAND METHYLATOR PHENOTYPE; METASTATIC COLORECTAL-CANCER; MICROSATELLITE INSTABILITY; V600E MUTATION; ADJUVANT THERAPY; MISMATCH REPAIR; KRAS MUTATION; IRINOTECAN; SURVIVAL; CAMPTOTHECIN;

D O I：

10.1158/1078-0432.CCR-11-2246

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose: Alterations in the RAS-RAF-MAP2K (MEK)-MAPK signaling pathway are major drivers in colorectal carcinogenesis. In colorectal cancer, BRAF mutation is associated with microsatellite instability (MSI), and typically predicts inferior prognosis. We examined the effect of BRAF mutation on survival and treatment efficacy in patients with stage III colon cancer. Methods: We assessed status of BRAF c.1799T>A (p.V600E) mutation and MSI in 506 stage III colon cancer patients enrolled in a randomized adjuvant chemotherapy trial [5-fluorouracil and leucovorin (FU/LV) vs. irinotecan (CPT11), FU and LV (IFL); CALGB 89803]. Cox proportional hazards model was used to assess the prognostic role of BRAF mutation, adjusting for clinical features, adjuvant chemotherapy arm, and MSI status. Results: Compared with 431 BRAF wild-type patients, 75 BRAF-mutated patients experienced significantly worse overall survival [OS; log-rank P = 0.015; multivariate HR = 1.66; 95% Cl: 1.05-2.63]. By assessing combined status of BRAF and MSI, it seemed that BRAF-mutated MSS (microsatellite stable) tumor was an unfavorable subtype, whereas BRAF wild-type MSI-high tumor was a favorable subtype, and BRAF-mutated MSI-high tumor and BRAF wild-type MSS tumor were intermediate subtypes. Among patients with BRAF-mutated tumors, a nonsignificant trend toward improved OS was observed for IFL versus FU/LV arm (multivariate HR = 0.52; 95% Cl: 0.25-1.10). Among patients with BRAF wild-type cancer, IFL conferred no suggestion of benefit beyond FU/LV alone (multivariate HR = 1.02; 95% Cl: 0.72-1.46). Conclusions: BRAF mutation is associated with inferior survival in stage III colon cancer. Additional studies are necessary to assess whether there is any predictive role of BRAF mutation for irinotecan-based therapy. Clin Cancer Res; 18(3); 890-900. (C) 2011 AACR.

引用

页码：890 / 900

页数：11

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[Anonymous], BIOCH BIOPHYS ACTA

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[Anonymous], 2011, PATHOL RES INT

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