Detection of microsatellite instability high (MSI-H) status by targeted plasma-based genotyping in metastatic breast cancer

We evaluate microsatellite instability-high (MSI-H) status with cell-free DNA (cfDNA) in metastatic breast cancer (MBC) and the association with clinico-genomic characteristics. Patients with MSI-H in cfDNA (Guardant360(®), 74 gene next-generation sequencing (NGS) with MBC are identified. We conduct a retrospective review. The median number of alterations and a median maximum mutant allelic fraction (MAF) in MSI-H and non-MSI-H cohorts are compared with Mann–Whitney U-test. Of 6718 patients with breast cancer with ≥1 plasma NGS alteration, 42 (0.63%) have MSI-H. A median number of genomic alterations per sample is 11 in MSI-H vs. 3 in non-MSI-H (Mann–Whitney U-test p < 0.0001) and the median maximum MAF is 16.8% in MSI-H vs. 2.6% in non-MSI-H (Mann–Whitney U-test p < 0.0001). The co-existing genomic landscape is heterogeneous. The median response duration for seven patients receiving immunotherapy is 92 days (range 29–273 days). CfDNA can identify MSI-H in MBC. Research is needed to validate immunotherapy usage in cfDNA-detected MSI-H MBC.