Detection of microsatellite instability high (MSI-H) status by targeted plasma-based genotyping in metastatic breast cancer
Neelima Vidula, Andrew Lipman, Shumei Kato, Caroline Weipert, Katherine Hesler, Georges Azzi, Ahmed Elkhanany, Dejan Juric, Estelamari Rodríguez, Colleen Faulkner, Paul Makhlouf, Kristin S. Price, Joyce O’Shaughnessy, Aditya Bardia
Abstract
Abstract 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.