Durable complete response with immune checkpoint inhibitor in breast cancer with high tumor mutational burden and APOBEC signature

Saranya Chumsri, Ethan S. Sokol, Aixa E. Soyano-Muller, Ricardo D. Parrondo, Gina A. Reynolds, Aziza Nassar, E. Aubrey Thompson

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Increasing data support the importance of preexisting host immune response and neoantigen burden for determining response to immune checkpoint inhibitors (ICIs). In lung cancer and melanoma, tumor mutational burden (TMB) has emerged as an independent biomarker for ICI response. However, the significance of TMB in breast cancer, particularly in the context of PD-L1 negativity, remains unclear. This report describes a patient with HER2-negative breast cancer with high TMB and an apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) trinucleotide signature; her disease was refractory to multiple lines of treatments but achieved durable complete response using ICIs and capecitabine. Additional analysis of the tumor revealed a low amount of stromal tumor-infiltrating lymphocytes (sTILs) and PD-L1 negativity, reflecting a poor preexisting host immune response. In collaboration with Foundation Medicine, comprehensive genomic profiling from 14,867 patients with breast cancer with the FoundationOne test was evaluated. Using the cutoff of $10 mutations/megabase (mut/Mb) for high TMB, PD-L1 positivity and TMB-high populations were not significantly overlapping (odds ratio, 1.02; P5.87). Up to 79% of TMB-high tumors with .20 mut/Mb were PD-L1–negative. Our study highlights that despite having low TILs and PD-L1 negativity, some patients may still experience response to ICIs.

Original languageEnglish (US)
Pages (from-to)517-521
Number of pages5
JournalJNCCN Journal of the National Comprehensive Cancer Network
Volume18
Issue number5
DOIs
StatePublished - May 2020

ASJC Scopus subject areas

  • Oncology

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