Comprehensive genomic profiling of Taiwanese triple negative breast cancers with medium- and large-sized sequencing panels: a comparative study implicating treatment allocations

Introduction: Comprehensive genomic profiling (CGP) is a molecular diagnostic tool with increasing use in cancer research and treatment. There are several commercialized CGP assays with variable targeted genes, while the trade-offs between medium- and large-sized panels to refine genomic profiling strategies, optimize resource allocation, and enhance clinical applications deserve evaluation.Methods: Triple-negative breast cancer (TNBC) patients from the VGH-TAYLOR study were initially assayed by a medium-sized CGP panel, and the remaining nucleic acid specimens were re-sequenced with a large-sized panel. Molecular profiling between the two sequencing panels was compared and reported.Results: A total of 108 breast cancers were successfully assayed using both platforms and 272 variants were reported at least once by either CGP. Variants reported were among actionable genes (AKT1, BRCA1/2, PALB2, ERBB2, PIK3CA, and PTEN) and TP53. The concordance rate between both medium- and large-sized panels was 34.6% and was enhanced to 58.9% after excluding polymorphisms, out-of-targeted region variants and those with low variant allele frequency (<10%), with variants among TP53, ERBB2, and PTEN boosted the most. A majority of discordance came from TSO500-detected only variants, especially for BRCA1, BRCA2, and PALB2.Conclusion: Only one-third of actionable mutations could be detected consistently between the medium- and large-sized CGP panels using the default analytical pipelines, while extensive bioinformatics analyses improved concordance substantially. The larger panel, detected more variants enhancing actionability. With more therapeutic targets revealed, CGP would be particularly impactful in refining strategies for TNBC management.