# Prevalence and mutational determinants of high tumor mutation burden in breast cancer

Source: https://onco.cc/key-papers/paper-barroso-sousa-breast-tmb-prevalence-ann-oncol-2020/  
OnCo record `paper-barroso-sousa-breast-tmb-prevalence-ann-oncol-2020` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Across nearly 4,000 breast cancers, one in twenty carried ten or more mutations per megabase, more often in triple-negative and metastatic tumours, and mostly because of APOBEC enzyme activity or mismatch repair failure.

## Summary

3,969 primary or metastatic breast cancer samples from six public genomic studies with exome or panel sequencing were classified as high TMB at 10 or more mutations per megabase; eight Dana-Farber patients were added. Median TMB was 2.63 mut/Mb and varied by subtype (HR-negative/HER2-negative above HER2-positive above HR-positive/HER2-negative) and sample type (metastatic above primary). Hypermutated tumours were found in 198 patients (5%), enriched in metastatic versus primary disease (8.4% versus 2.9%). APOBEC activity (59.2%) and mismatch repair deficiency (36.4%) were the commonest mutational processes; three hypermutated patients treated with pembrolizumab-based therapy had objective durable responses.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Journal: Annals of Oncology
- Year: 2020
- DOI: 10.1016/j.annonc.2019.11.010
- Authors: Barroso-Sousa R, Jain E, Cohen O, et al.
- Findings: Hypermutation (10 or more mut/Mb) in 5% of breast cancers; 8.4% metastatic versus 2.9% primary.; Median TMB 2.63 mut/Mb, highest in HR-negative/HER2-negative tumours.; APOBEC 59.2% and mismatch repair deficiency 36.4% of hypermutated tumours.
- What it means: TMB-high is uncommon but not negligible in TNBC, rises at relapse, and the tumour-agnostic pembrolizumab indication makes it worth measuring on a metastatic biopsy.
- Caveats: Mixed exome and panel data; panel TMB estimates are not interchangeable with exome.; Subtype-specific prevalence is described qualitatively in the abstract.

## Sources

- Barroso-Sousa et al., Ann Oncol 2020: prevalence of high tumour mutation burden in 3,969 breast cancers: https://doi.org/10.1016/j.annonc.2019.11.010
- PubMed: https://pubmed.ncbi.nlm.nih.gov/32067680/

## Connected records

- biomarkers: [TMB-high (tumour mutational burden >= 10 mutations per megabase)](https://onco.cc/biomarkers/tmb-high/)
- cancers: [Breast cancer (all types)](https://onco.cc/cancers/breast-cancer/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- technologies: [Tumour mutational burden testing](https://onco.cc/technologies/tmb-testing/)
- institutions: [Dana-Farber Brigham Cancer Center](https://onco.cc/institutions/dana-farber/)
- terms: [Mutational signature](https://onco.cc/terms/mutational-signature/), [Tumour mutational burden (TMB)](https://onco.cc/terms/tmb/)
- people: [Eric P. Winer](https://onco.cc/people/eric-winer/), [Nancy U. Lin](https://onco.cc/people/nancy-lin/), [Sara M. Tolaney](https://onco.cc/people/sara-tolaney/)
- journals: [Annals of Oncology](https://onco.cc/journals/annals-of-oncology/)
- drugs: [FoundationOne CDx / Liquid CDx](https://onco.cc/drugs/foundationone-cdx/)

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