{"entity":{"id":"paper-barroso-sousa-tmb-pten-ici-mtnbc-ccr-2020","kind":"paper","name":"Tumor mutational burden and PTEN alterations as molecular correlates of response to PD-1/L1 blockade in metastatic triple-negative breast cancer","aka":[],"tldr":"In 62 women with metastatic triple-negative cancer treated with immunotherapy, high mutation burden (18%) went with a year of progression-free time versus under four months, while PTEN loss (29%) went with almost no responses.","summary":"62 patients with metastatic TNBC who consented to targeted DNA sequencing and were treated with anti-PD-1/L1 therapy on trials at Dana-Farber (2014 to 2019) alone (23%), with targeted therapy (19%) or chemotherapy (58%). High TMB (10 or more nonsynonymous mutations/Mb; 18%) was associated with longer progression-free survival (12.5 versus 3.7 months; P 0.04); PTEN alterations (nonsynonymous mutation or one- or two-copy deletion; 29%) with lower objective response (6% versus 48%), shorter PFS (2.3 versus 6.1 months) and shorter overall survival (9.7 versus 20.5 months), independent of performance status, prior lines, regimen, visceral disease and PD-L1, and not seen in chemotherapy-treated (90) or non-immunotherapy (169) cohorts.","asOf":"2026-09-24","links":[{"label":"Barroso-Sousa et al., Clin Cancer Res 2020: TMB and PTEN alterations and checkpoint response in 62 metastatic TNBC patients","url":"https://doi.org/10.1158/1078-0432.CCR-19-3507"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32019858/"}],"tags":[],"related":["tmb-high","pten-alteration"],"cancers":["tnbc","tnbc-metastatic"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":["pten","pdl1","pd1"],"drugs":[],"companies":[],"institutions":["dana-farber"],"pathways":[],"terms":["tmb"],"trials":[],"people":["sara-tolaney","nancy-lin"],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2020,"doi":"10.1158/1078-0432.CCR-19-3507","pmid":"32019858","authors":"Barroso-Sousa R, Keenan TE, Pernas S, et al.","paperType":"observational","findings":["High TMB in 18%: PFS 12.5 versus 3.7 months.","PTEN alterations in 29%: response 6% versus 48%, overall survival 9.7 versus 20.5 months.","Associations independent of PD-L1 and absent in non-immunotherapy cohorts."],"whatItMeans":"PTEN loss, the most common PI3K-pathway lesion in TNBC, may mark primary immunotherapy resistance, and TMB may add to PD-L1 in choosing who gets checkpoint blockade.","caveats":["62 patients across heterogeneous trials; hypothesis-generating.","Panel-derived TMB."],"changedPractice":false,"participants":62},"route":"/key-papers/paper-barroso-sousa-tmb-pten-ici-mtnbc-ccr-2020/","neighbours":{"biomarker":[{"id":"pten-alteration","kind":"biomarker","name":"PTEN alteration (sequencing) and PTEN loss (IHC)","route":"/biomarkers/pten-alteration/"},{"id":"tmb-high","kind":"biomarker","name":"TMB-high (tumour mutational burden >= 10 mutations per megabase)","route":"/biomarkers/tmb-high/"}],"cancer":[{"id":"tnbc-metastatic","kind":"cancer","name":"Metastatic triple-negative breast cancer","route":"/cancers/tnbc-metastatic/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}],"target":[{"id":"pd1","kind":"target","name":"PD-1","route":"/targets/pd1/"},{"id":"pdl1","kind":"target","name":"PD-L1","route":"/targets/pdl1/"},{"id":"pten","kind":"target","name":"PTEN","route":"/targets/pten/"}],"institution":[{"id":"dana-farber","kind":"institution","name":"Dana-Farber Brigham Cancer Center","route":"/institutions/dana-farber/"}],"term":[{"id":"tmb","kind":"term","name":"Tumour mutational burden (TMB)","route":"/terms/tmb/"}],"person":[{"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":"clinical-cancer-research","kind":"journal","name":"Clinical Cancer Research","route":"/journals/clinical-cancer-research/"}]}}