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Genomic evaluation of tumor mutational burden-high (TMB-H) versus TMB-low (TMB-L) metastatic breast cancer to reveal unique mutational features

Authors:

Sarah Sammons, Andrew Elliott, Jeremy Meyer Force, Nicholas C. DeVito, Paul Kelly Marcom, Sandra M. Swain, Antoinette R. Tan, Evanthia T. Roussos Torres, Jia Zeng, Mustafa Khasraw, Justin M. Balko, Wolfgang Michael Korn, Carey K. Anders

Abstract

Background:
Tumor mutational burden (TMB) has emerged as an imperfect biomarker of immune checkpoint inhibition (ICI) outcomes in solid tumors. Despite the approval for pembrolizumabin all TMB-high (TMB-H) solid tumors, the optimal clinical approach to TMB-H advanced/metastatic breast cancer (MBC) is unknown with sparse prospective data.

We hypothesized that TMB-H MBC will have unique genomic alterations, mutational signatures, and immune profiles compared to TMB-low (TMB-L) breast cancer that could inform novel therapeutic approaches.

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