npj Breast Cancer (Nov 2022)

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 Rodriguez,
  • Colleen Faulkner,
  • Paul Makhlouf,
  • Kristin Price,
  • Joyce O’Shaughnessy,
  • Aditya Bardia

DOI
https://doi.org/10.1038/s41523-022-00490-2
Journal volume & issue
Vol. 8, no. 1
pp. 1 – 7

Abstract

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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.