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Cancer Genomics and Diagnostics / Cancer Cells and Metastasis / Breast Cancer Treatment Studies · Journal article
JAMA Oncology · August 13, 2026
Encouraging direction, but not yet definitive.
In this prospective prognostic analysis of 159 TNBC patients, tissue-free ctDNA detection during post-treatment surveillance was strongly associated with recurrence risk (HR 27.2) and showed comparable lead times to recurrence versus tumor-informed assays. While the tissue-free assay performed well and showed potential for clinical implementation when tumor tissue is unavailable, the study relies on surrogate measures (lead time, detection concordance) rather than definitive clinical trial outcomes, and results require prospective validation.
Prospective prognostic and exploratory analysis within a multicenter phase 2 clinical study. Patients with TNBC at moderate to high risk of recurrence participating in the ctDNA surveillance period of c-TRAK TN. Mean age 51.4 years (SD 11.4, range 25–78), all female.. Intervention: Tissue-free circulating tumor DNA (ctDNA) detection using digital polymerase chain reaction (dPCR) leveraging cancer differential methylation patterns. Compared with: Digital polymerase chain reaction (dPCR) and whole-exome sequencing–powered multivariant tumor-informed assays. n = 159. Multicenter study; specific sites not enumerated in the provided text.
Tissue-free ctDNA detected in 54 of 159 patients (34.0%), strongly associated with recurrence (HR 27.2; 95% CI 13.7–54.2; P<0.001) Among 42 patients with ctDNA detected by both tissue-free and dPCR, tissue-free detection was earlier in 14 patients (33.3%); dPCR was never earlier Median lead time to recurrence: tissue-free 7.9 months (95% CI 6.1–10.5) vs dPCR 5.8 months (95% CI 3.3–10.0); HR 0.57 (95% CI 0.34–0.95; P=0.03)
Safety was not reported in the material analysed. Check the source before drawing any conclusion about harm.
This study supports the use of tissue-free ctDNA assays for molecular residual disease detection in TNBC when tumor tissue is unavailable, as they show comparable performance to tumor-informed assays. However, results are from a prognostic analysis within a phase 2 study and should prompt a dedicated prospective clinical trial before routine adoption in treatment selection.
A well-designed prospective prognostic study in a defined population showing tissue-free ctDNA strongly predicts recurrence and performs comparably to tumor-informed assays, but uses surrogate endpoints (lead time, detection concordance) rather than direct clinical outcomes, and requires confirmation in a prospective trial.
As stated by the source record.
Quoted from the source exactly as published.
This study supports the use of tissue-free ctDNA assays for molecular residual disease detection in TNBC when tumor tissue is unavailable, as they show comparable performance to tumor-informed assays. However, results are from a prognostic analysis within a phase 2 study and should prompt a dedicated prospective clinical trial before routine adoption in treatment selection.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
Importance 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. Objective 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. Design, Setting, and Participants 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. Intervention or Exposure Tissue-free assay leverages cancer differential methylation patterns to detect ctDNA. Main Outcome and Measures Recurrence-free survival by tissue-free ctDNA detection status. Comparison between tissue-free ctDNA detection and both dPCR and whole-exome sequencing−powered multivariant tumor-informed assays. Results 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; P lt;.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; P =.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; P =.15). Conclusion and Relevance 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.
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