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:10.1038/s41523-022-00490-2

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

NPJ Breast Cancer. 2022 Nov 4;8(1):117. doi: 10.1038/s41523-022-00490-2.

Authors

Affiliations

¹ Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA. nvidula@mgh.harvard.edu.
² Florida Cancer Specialists, Sun City Center, FL, USA.
³ University of California San Diego, San Diego, CA, USA.
⁴ Guardant Health, Redwood, CA, USA.
⁵ Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
⁶ Bienes Cancer Center, Fort Lauderdale, FL, USA.
⁷ University of Alabama at Birmingham, Birmingham, AL, USA.
⁸ Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA.
⁹ Texas Oncology-Baylor Charles A. Sammons Cancer Center, Dallas, TX, USA.

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.