HER2/HER3 and PIK3CA Mutations in Colorectal Cancer are Associated with Microsatellite Instability

By Anthony M Magliocco MD

 

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A recent study by Loree reported in the  Journal of the National Cancer Institute, found that ERBB2/ERBB3 mutations in colorectal cancer are associated with the presence of MSI microsatellite instability and PIK3CA mutation.

Study Details- Retrospective analysis of Colorectal Cancer Cases from two Cohorts

The study involved retrospective analysis of 419 patients from The University of Texas MD Anderson Cancer Center (MDACC) and 619 patients from the Nurses’ Health Study (NHS)/Health Professionals Follow-Up Study (HPFS) with stage I to IV disease, with tissue sequencing, clinicopathologic, mutational, and colorectal cancer consensus molecular subtype (CMS) profiles of patients with ERBB2/ERBB3 mutations. The circulating tumor DNA profile associated with ERBB2mutation was also investigated in an additional cohort of 1,623 patients with circulating tumor DNA assay results.

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Factors Associated With ERBB2/ERBB3 Mutation

Mutations were found in over 5% of cases and were not associated with age, location or stage of tumor. ERBB2 mutations were associated with shortend survival HR 1.82 but not ERBB3

The investigators concluded, “[Microsatellite instability] and PIK3CA mutations are associated with ERBB2/ERBB3 mutations. Co-occurring PIK3CA mutations may represent a second hit to oncogenic signaling that needs consideration when targeting ERBB2/ERBB3.”

 

The findings are interesting in that mutated ERBB2 is potentially an actionable target.