Mutations of the BRAF and KRAS genes may be associated with worse outcomes in certain patients with colon cancer, according to a new study.
The use of BRAF and KRAS as prognostic indicators in colon cancer has been a controversial topic, possible due to a lack of information about how DNA mismatch repair status affects the prognostic value of these genes.
The PETACC-8 trial, conducted between 2005 and 2009, aimed to test the effectiveness of combination chemotherapy with or without cetuximab added. The trial included 2559 patients with stage 3 colon cancer who underwent surgical resection and were randomly assigned a treatment regimen of combination chemotherapy with cetuximab or combination chemotherapy without cetuzimab. Ultimately, investigators concluded that the addition of cetuximab to combination chemotherapy had no significant effect on outcomes.
In a later study, published in JAMA Oncology, researchers examined patient data from the PETACC-8 trial to evaluate the prognostic value of BRAF and KRAS mutations in patients with tumors either positive or negative for microsatellite instability phenotype, a biomarker of defective mismatch repair.
Of the trial participants, 588 and 148 were found to have either KRAS or BRAF mutations, respectively. Overall, KRAS mutation–positive patients were found to have shorter disease-free survival (DFS) and overall survival (OS).
In a subgroup analysis, the presence of mutations of either gene in tumors that were microsatellite-stable was associated with poorer outcomes. In those whose tumors were of the microsatellite instability phenotype, KRAS did not appear to have any effect on outcomes, whereas the BRAF mutation was associated with significantly improved DFS but no change in OS.
The researchers concluded that the BRAF and KRAS mutations were associated with significantly shorter DFS and OS in patients with microsatellite-stable tumors, but not in those with defective mismatch repair systems. Therefore, the mutations could be used as prognostic indicators in the former subset of patients with colon cancer. The findings indicate that future research will need to give more attention to accounting for mismatch repair status when evaluating the prognostic value of BRAF and KRAS status in colon cancer.
