{"entity":{"id":"paper-barroso-sousa-breast-tmb-prevalence-ann-oncol-2020","kind":"paper","name":"Prevalence and mutational determinants of high tumor mutation burden in breast cancer","aka":[],"tldr":"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.","asOf":"2026-09-24","links":[{"label":"Barroso-Sousa et al., Ann Oncol 2020: prevalence of high tumour mutation burden in 3,969 breast cancers","url":"https://doi.org/10.1016/j.annonc.2019.11.010"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32067680/"}],"tags":[],"related":["tmb-high"],"cancers":["tnbc","breast-cancer"],"sections":[],"technologies":["tmb-testing"],"targets":[],"drugs":[],"companies":[],"institutions":["dana-farber"],"pathways":[],"terms":["tmb","mutational-signature"],"trials":[],"people":["nancy-lin","sara-tolaney","eric-winer"],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2020,"doi":"10.1016/j.annonc.2019.11.010","pmid":"32067680","authors":"Barroso-Sousa R, Jain E, Cohen O, et al.","paperType":"observational","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."],"whatItMeans":"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."],"changedPractice":false,"participants":3969},"route":"/key-papers/paper-barroso-sousa-breast-tmb-prevalence-ann-oncol-2020/","neighbours":{"biomarker":[{"id":"tmb-high","kind":"biomarker","name":"TMB-high (tumour mutational burden >= 10 mutations per megabase)","route":"/biomarkers/tmb-high/"}],"cancer":[{"id":"breast-cancer","kind":"cancer","name":"Breast cancer (all types)","route":"/cancers/breast-cancer/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"technology":[{"id":"tmb-testing","kind":"technology","name":"Tumour mutational burden testing","route":"/technologies/tmb-testing/"}],"institution":[{"id":"dana-farber","kind":"institution","name":"Dana-Farber Brigham Cancer Center","route":"/institutions/dana-farber/"}],"term":[{"id":"mutational-signature","kind":"term","name":"Mutational signature","route":"/terms/mutational-signature/"},{"id":"tmb","kind":"term","name":"Tumour mutational burden (TMB)","route":"/terms/tmb/"}],"person":[{"id":"eric-winer","kind":"person","name":"Eric P. Winer","route":"/people/eric-winer/"},{"id":"nancy-lin","kind":"person","name":"Nancy U. Lin","route":"/people/nancy-lin/"},{"id":"sara-tolaney","kind":"person","name":"Sara M. Tolaney","route":"/people/sara-tolaney/"}],"journal":[{"id":"annals-of-oncology","kind":"journal","name":"Annals of Oncology","route":"/journals/annals-of-oncology/"}],"drug":[{"id":"foundationone-cdx","kind":"drug","name":"FoundationOne CDx / Liquid CDx","route":"/drugs/foundationone-cdx/"}]}}