The implication of BRAF mutation in advanced colorectal cancer

Advanced colorectal cancer (CRC) is frequently a lethal disease. Mutations in the BRAF gene is a key driver in CRC pathogenesis and confers a poor prognosis. To date, Irish data on this molecular subtype of CRC is lacking.

Our aim was to compare the natural history of Irish patients with BRAF (BRAF^MUT) metastatic CRC with a control group of metastatic CRC patients without BRAF mutation (BRAF^WT wild- type).

A retrospective observational analysis of advanced CRC patients with known BRAF^MUT was conducted by chart review. BRAF^MUT patients were identified from the Cork University Hospital (CUH) histopathology database. Controls with known BRAF^WT were randomly selected from the database. Demographic characteristics and clinicopathological data were recorded. Survival was assessed with Kaplan-Meier curve/Cox proportional hazard models.

Twenty patients with BRAF^MUT and 36 with BRAF^WT were studied. BRAF^MUT were more likely female (75% vs 33%, p = 0.007) and right-sided (65% vs 31.4%, p = 0.033). Median overall survival was lower in BRAF^MUT group (17.3 months (95% CI 0-40.8)) compared to patients with BRAF^WT (median survival not reached, log rank p = 0.001). On multivariate analysis, BRAF^MUT was independently associated with an increased risk of mortality (HR 12.76 (95% CI 3.15-51.7), p < 0.001).

BRAF^MUT advanced colorectal cancer was associated with significantly reduced overall survival in this Irish CRC population. Knowledge of mutation status should now be considered standard of care and should dictate management. Surgeons should be aware of this genetic signature as the natural history of the disease may mitigate against an aggressive surgical strategy. A prospective study should be conducted to further corroborate these findings.