Kefah Mokbel, Chair of Breast Cancer Surgery at London Breast Institute, shared on LinkedIn:
“Post-surgical ctDNA carried a 100% positive predictive value for metastatic recurrence in the extended TRACER analysis.
Elliott and colleagues (ESMO Open, 2026) report extended follow-up of 121 patients with early breast cancer treated with neoadjuvant systemic therapy, monitored using an ultrasensitive tumour-informed structural variant digital PCR assay (LoD95 5.2 ppm). Median follow-up 4.2 years; 767 plasma samples.
Key findings:
- Every patient with detectable ctDNA in the adjuvant setting developed metastatic recurrence (22 of 22). Sensitivity 95%, specificity 100%, NPV 99% for distant recurrence.
- Median lead time from ctDNA detection to clinical recurrence was 346 days (range 0 to 1937).
- Baseline detection was 95% overall and 90% in ER-positive/HER2-negative disease, addressing a known weakness of first-generation SNV-based assays in this subtype.
- ctDNA clearance during NST was associated with markedly improved distant recurrence-free interval (HR 0.20, 95% CI 0.079 to 0.48).
- Tumour fraction at first detection stratified risk in a graded fashion, with higher TF predicting shorter time to recurrence. Detection alone is not the whole signal.
- 79% of primary tumour-specific structural variants remained detectable at recurrence (median 92%), supporting SVs as stable genomic fingerprints under therapeutic pressure.
Where I would urge caution: this is retrospective, single-centre, and results were never returned to clinicians. Lead time is not benefit. The cohort predates chemoimmunotherapy and adjuvant CDK4/6 inhibition, both of which will alter ctDNA kinetics. The metastatic monitoring component rests on nine patients.
The specificity is remarkable and the biology is sound. What remains unproven is whether acting on a positive result changes outcome. That answer requires prospective interventional trials, not more observational cohorts.”
Title: Longitudinal ctDNA tracking in early and recurrent breast cancer using an ultrasensitive structural variant-based assay: an extended analysis from the TRACER study
Authors: Mitchell Elliott, J. Roh, T. Bird, M. Li, M.B. Nadler, E. Amir, V. Kumar, C. Yu, M. Alcaide, S. Birkeälv, V. Hafstad, E. Gray, E.C. de Bruin, W. Levin, L.L. Siu, P.L. Bedard, H.K. Berman, K. Howarth, D.W. Cescon
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