{"entity":{"id":"paper-radovich-ctdna-ctc-bre12-158-jama-oncol-2020","kind":"paper","name":"Association of Circulating Tumor DNA and Circulating Tumor Cells After Neoadjuvant Chemotherapy With Disease Recurrence in Patients With Triple-Negative Breast Cancer: Preplanned Secondary Analysis of the BRE12-158 Randomized Clinical Trial","aka":[],"tldr":"In 196 women with triple-negative breast cancer left with residual tumour after pre-surgery chemotherapy, finding tumour DNA in the blood after surgery tripled the risk of distant relapse and quadrupled the risk of death; at two years 56 percent versus 81 percent were free of distant disease.","summary":"Radovich, Jiang, Hancock, Chitambar and colleagues report a preplanned secondary analysis of BRE12-158, a phase 2 trial that randomised patients with early-stage triple-negative breast cancer and residual disease after neoadjuvant chemotherapy to genomically directed therapy or physician's choice; 196 patients had blood drawn at treatment assignment, with ctDNA (FoundationACT or FoundationOne Liquid) analysed for survival in 142 and circulating tumour cells in 123, median follow-up 17.2 months. ctDNA detection was associated with inferior distant disease-free survival (median 32.5 months versus not reached; hazard ratio 2.99, 95 percent confidence interval 1.38 to 6.48, p=0.006; two-year probability 56 versus 81 percent), disease-free survival (2.67) and overall survival (4.16, 1.66 to 10.42, p=0.002). Patients positive for both ctDNA and circulating tumour cells had a distant disease-free survival hazard ratio of 5.29 versus double-negative patients (two-year probability 52 versus 89 percent) and overall survival hazard ratio 8.60.","asOf":"2026-09-24","links":[{"label":"JAMA Oncol 2020","url":"https://doi.org/10.1001/jamaoncol.2020.2295"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/32644110/"},{"label":"ClinicalTrials.gov NCT02101385","url":"https://clinicaltrials.gov/study/NCT02101385"}],"tags":["tnbc-evidence"],"related":["ctdna-tests","paper-turner-c-trak-tn-ctdna-pembrolizumab-ann-oncol-2023","ctdna-mrd-positive"],"cancers":["tnbc","tnbc-early"],"sections":[],"technologies":["liquid-biopsy","mrd-testing"],"targets":[],"drugs":["foundationone-cdx"],"companies":["foundation-medicine"],"institutions":[],"pathways":[],"terms":["ctdna","mrd","rcb","hazard-ratio"],"trials":[],"people":[],"bottlenecks":["b-dormancy-mrd","b-biomarker-validation"],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2020,"doi":"10.1001/jamaoncol.2020.2295","pmid":"32644110","authors":"Radovich M, Jiang G, Hancock BA, et al.","paperType":"rct","findings":["ctDNA detection after neoadjuvant chemotherapy: distant disease-free survival hazard ratio 2.99 (95 percent CI 1.38 to 6.48), p=0.006; two-year probability 56 vs 81 percent.","Overall survival hazard ratio 4.16 (1.66 to 10.42), p=0.002.","ctDNA and circulating tumour cell double positivity: distant disease-free survival hazard ratio 5.29; two-year probability 52 vs 89 percent."],"whatItMeans":"The proof that a blood test can split residual-disease patients into those likely to relapse and those likely cured, the premise of the ctDNA-guided adjuvant idea; no completed trial has yet acted on the result.","caveats":["Short follow-up (17.2 months) and a tumour-agnostic assay less sensitive than tumour-informed tests.","Secondary analysis of a trial whose primary comparison was negative."],"changedPractice":false,"participants":196},"route":"/key-papers/paper-radovich-ctdna-ctc-bre12-158-jama-oncol-2020/","neighbours":{"roadmap":[{"id":"ctdna-tests","kind":"roadmap","name":"ctDNA tests roadmap: from a curiosity in plasma to blood tests that decide treatment","route":"/roadmaps/ctdna-tests/"},{"id":"tnbc-roadmap","kind":"roadmap","name":"Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem","route":"/roadmaps/tnbc-roadmap/"}],"paper":[{"id":"paper-turner-c-trak-tn-ctdna-pembrolizumab-ann-oncol-2023","kind":"paper","name":"Results of the c-TRAK TN trial: a clinical trial utilising ctDNA mutation tracking to detect molecular residual disease and trigger intervention in patients with moderate- and high-risk early-stage triple-negative breast cancer","route":"/key-papers/paper-turner-c-trak-tn-ctdna-pembrolizumab-ann-oncol-2023/"}],"biomarker":[{"id":"ctdna-mrd-positive","kind":"biomarker","name":"ctDNA MRD positivity (molecular residual disease after curative treatment)","route":"/biomarkers/ctdna-mrd-positive/"}],"cancer":[{"id":"tnbc-early","kind":"cancer","name":"Early triple-negative breast cancer","route":"/cancers/tnbc-early/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"technology":[{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/"},{"id":"mrd-testing","kind":"technology","name":"MRD / molecular residual disease testing","route":"/technologies/mrd-testing/"}],"drug":[{"id":"foundationone-cdx","kind":"drug","name":"FoundationOne CDx / Liquid CDx","route":"/drugs/foundationone-cdx/"}],"company":[{"id":"foundation-medicine","kind":"company","name":"Foundation Medicine (Roche)","route":"/companies/foundation-medicine/"}],"term":[{"id":"ctdna","kind":"term","name":"Circulating tumour DNA (ctDNA)","route":"/terms/ctdna/"},{"id":"hazard-ratio","kind":"term","name":"Hazard ratio (HR)","route":"/terms/hazard-ratio/"},{"id":"mrd","kind":"term","name":"Minimal / molecular residual disease (MRD)","route":"/terms/mrd/"},{"id":"rcb","kind":"term","name":"Residual cancer burden (RCB)","route":"/terms/rcb/"}],"bottleneck":[{"id":"b-biomarker-validation","kind":"bottleneck","name":"Biomarkers are not validated or standardised","route":"/bottlenecks/b-biomarker-validation/"},{"id":"b-dormancy-mrd","kind":"bottleneck","name":"Dormant cells and minimal residual disease","route":"/bottlenecks/b-dormancy-mrd/"}],"journal":[{"id":"jama-oncology","kind":"journal","name":"JAMA Oncology","route":"/journals/jama-oncology/"}],"idea":[{"id":"idea-tnbc-ctdna-guided-adjuvant-decisions","kind":"idea","name":"ctDNA-guided adjuvant decisions after residual disease: escalate the positive, spare the negative","route":"/ideas/idea-tnbc-ctdna-guided-adjuvant-decisions/"}]}}