{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T02:37:52Z","timestamp":1793759872541,"version":"4.6.1"},"reference-count":24,"publisher":"American Medical Association (AMA)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Oncol"],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:sec id=\"ab-coi260043-4\">\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>Molecular residual disease (MRD) detection has potential to transform the selection of adjuvant therapy. Most evidence is from tumor-informed assays. Tissue-free assays not requiring sequencing of the primary tumor may simplify workflows if they offer accuracy similar to that of tumor-informed assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-coi260043-5\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate tissue-free circulating tumor DNA (ctDNA) analysis in patients with triple negative breast cancer (TNBC) and compare the tissue-free assay with tumor-informed assay results.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-coi260043-6\">\n                    <jats:title>Design, Setting, and Participants<\/jats:title>\n                    <jats:p>This was a prognostic and exploratory analysis of patients with TNBC at moderate to high risk of recurrence who were participating in the ctDNA surveillance period of c-TRAK TN, a multicenter phase 2 clinical study. Plasma samples were collected from participants every 3 months for up to 2 years after the completion of adjuvant therapy and analyzed prospectively with digital polymerase chain reaction (dPCR). Data for the analysis were from a database lock on September 28, 2021, with subsequent follow-up through January 18, 2023. Data were analyzed from July 2025 to May 2026.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-coi260043-7\">\n                    <jats:title>Intervention or Exposure<\/jats:title>\n                    <jats:p>Tissue-free assay leverages cancer differential methylation patterns to detect ctDNA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-coi260043-8\">\n                    <jats:title>Main Outcome and Measures<\/jats:title>\n                    <jats:p>Recurrence-free survival by tissue-free ctDNA detection status. Comparison between tissue-free ctDNA detection and both dPCR and whole-exome sequencing\u2212powered multivariant tumor-informed assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-coi260043-9\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The analysis included 1026 plasma samples from 159 patients (mean [SD; range] age, 51.4 [11.4; 25.0-78.0] years; 159 females [100%]). The tissue-free assay detected ctDNA in 54 patients (34.0%), with detection strongly associated with risk of recurrence (HR, 27.2; 95% CI, 13.7-54.2;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009&amp;amp;lt;\u2009.001). Among patients with ctDNA detected by both the tissue-free assay and dPCR (42 patients [26%]), tissue-free detection occurred at an earlier time point in 14 patients (33.3%); dPCR detection occurred before tissue-free detection in no patients. Median lead time to recurrence was 7.9 (95% CI, 6.1-10.5) months for tissue-free vs 5.8 (95% CI, 3.3-10.0) months for dPCR (HR, 0.57; 95% CI, 0.34-0.95;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009=\u2009.03). Concordance between tissue-free and multivariant tumor-informed assays was good. Among patients detected by both assays (41 of 133), 12 of 41 (29.3%) had ctDNA detected earlier by multivariant tumor-informed assay with 1 (2.4%) earlier by the tissue-free assay. Median lead times to recurrence were 7.6 (95% CI, 4.6-10.5) months with tissue-free and 7.1 (95% CI, 5.7-10.0) months with multivariant tumor-informed assay (HR, 1.46; 95% CI, 0.87-2.44;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009=\u2009.15).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-coi260043-10\">\n                    <jats:title>Conclusion and Relevance<\/jats:title>\n                    <jats:p>In this prognostic study, tissue-free ctDNA detection during surveillance was strongly prognostic for recurrence in patients with TNBC. Comparable lead times between the tissue-free and multivariant tumor-informed assays support tissue-free MRD detection in a clinical trial setting, permitting ctDNA testing when tissue is not available.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1001\/jamaoncol.2026.2833","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T15:30:25Z","timestamp":1786635025000},"page":"1098","source":"Crossref","is-referenced-by-count":3,"title":["Tissue-Free vs Tumor-Informed ctDNA Assays for Molecular Residual Disease Detection in Early Triple Negative Breast Cancer"],"prefix":"10.1001","volume":"12","author":[{"given":"Niamh","family":"Cunningham","sequence":"first","affiliation":[{"name":"The Ralph Lauren Centre for Breast Cancer Research, Royal Marsden Hospital, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosalind J.","family":"Cutts","sequence":"additional","affiliation":[{"name":"Breast Cancer Now Toby Robins Research 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UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Waters","sequence":"additional","affiliation":[{"name":"Velindre Cancer Centre, Velindre University NHS Trust, Cardiff, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Palmieri","sequence":"additional","affiliation":[{"name":"The Clatterbridge Cancer Centre NHS Foundation Trust, Liverpool, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Winter","sequence":"additional","affiliation":[{"name":"Weston Park Cancer Centre, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Bliss","sequence":"additional","affiliation":[{"name":"Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, 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