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Updated: Jul 19, 2025
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Tumor Mutational Burden in Breast Cancer: Current Evidence, Challenges, and Opportunities
Romualdo Barroso-Sousa1,2, Jana Priscila Pacífico1,2, Sarah Sammons3,4,5
1Dasa Institute for Education and Research (IEPD), Brasilia 71635-580, DF, Brazil.
Abstract:
Tumor mutational burden (TMB) correlates with tumor neoantigen burden, T cell infiltration, and response to immune checkpoint inhibitors in many solid tumor types. Based on data from the phase II KEYNOTE-158 study, the anti-PD-1 antibody pembrolizumab was granted approval for treating patients with advanced solid tumors and TMB ≥ 10 mutations per megabase. However, this trial did not include any patients with metastatic breast cancer; thus, several questions remain unanswered about the true role of TMB as a predictive biomarker of benefit to immune checkpoint inhibitor therapy in breast cancer. In this review, we will discuss the challenges and opportunities in establishing TMB as a predictive biomarker of benefit to immunotherapy in metastatic breast cancer.
Insights
Tumor mutational burden (TMB) is a biomarker for immunotherapy response in many cancers. Its role in metastatic breast cancer requires further investigation to guide treatment decisions.
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- Tumor mutational burden (TMB) is linked to neoantigen load, T cell infiltration, and response to immune checkpoint inhibitors (ICIs) in various solid tumors.
- Pembrolizumab, an anti-PD-1 antibody, is approved for advanced solid tumors with TMB ≥ 10 mutations/megabase based on the KEYNOTE-158 study.
- The KEYNOTE-158 study excluded patients with metastatic breast cancer, leaving its role as a predictive biomarker for ICI therapy in this population unclear.
Purpose of the Study:
- To review the current understanding of TMB in metastatic breast cancer.
- To discuss the challenges and opportunities in establishing TMB as a predictive biomarker for immunotherapy in metastatic breast cancer.
Main Methods:
- Literature review of studies investigating TMB and immunotherapy in metastatic breast cancer.
- Analysis of existing clinical trial data and research findings.
Main Results:
- TMB's correlation with treatment response in breast cancer is not fully established.
- Further research is needed to validate TMB as a predictive biomarker in this specific patient group.
Conclusions:
- Establishing TMB as a reliable predictive biomarker for immunotherapy in metastatic breast cancer presents significant challenges.
- Identifying and overcoming these challenges is crucial for optimizing immunotherapy strategies in breast cancer patients.
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