[BRAF V600E-mutant colorectal cancers: Where are we?]

Area of Science:

• Oncology
• Genetics
• Cancer Research

Background:

• The BRAF^V600E mutation occurs in 8% of colorectal cancers (CRC), correlating with specific tumor characteristics and poorer outcomes.
• BRAF-mutant CRCs often present in the right colon, are poorly differentiated, mucinous, and affect older females, with higher rates of lymph node and peritoneal metastasis.

Purpose of the Study:

• To outline the clinical implications and management strategies for BRAF^V600E-mutated colorectal cancer.
• To emphasize the importance of MSI testing in BRAF-mutant metastatic CRC for immunotherapy selection.

Main Methods:

• Review of clinical presentation, prognostic factors, and treatment guidelines for BRAF^V600E-mutated CRC.
• Analysis of treatment efficacy based on MSI status and disease stage (localized vs. metastatic).

Main Results:

• BRAF^V600E mutation is linked to sporadic MSI in 20-40% of CRCs.
• In localized disease, BRAF^V600E does not alter adjuvant treatment.
• In metastatic CRC, MSI testing guides immunotherapy; for non-MSI, first-line chemotherapy with bevacizumab is an option, with potential anti-EGFR addition for tumor response.
• Surgical resection of hepatic metastases is recommended, as BRAF^V600E is not a recurrence risk factor.

Conclusions:

• Systematic MSI screening is vital for BRAF-mutant metastatic CRC to enable immunotherapy.
• For non-MSI metastatic CRC, established chemotherapy regimens and targeted therapies like encorafenib, binimetinib, and cetuximab offer improved outcomes.
• Surgical management of metastases should be considered irrespective of BRAF^V600E status.