# 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

Source: https://onco.cc/key-papers/paper-turner-c-trak-tn-ctdna-pembrolizumab-ann-oncol-2023/  
OnCo record `paper-turner-c-trak-tn-ctdna-pembrolizumab-ann-oncol-2023` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The UK trial that watched 161 women with early triple-negative breast cancer by three-monthly blood tests for tumour DNA: 27 percent tested positive within a year, but by then nearly three quarters already had visible metastases, and none of the five who started pembrolizumab cleared the DNA. The lesson was to test earlier and more sensitively.

## Summary

c-TRAK TN (Turner, Swift, Jenkins, Kilburn and colleagues), a multicentre phase 2 trial with prospective ctDNA surveillance by digital PCR, enrolled patients with early-stage triple-negative breast cancer and residual disease after neoadjuvant chemotherapy, or stage II to III disease after adjuvant chemotherapy, for three-monthly sampling to 12 months (18 if samples were missed during the pandemic). ctDNA-positive patients were randomised 2:1 to intervention (staging scans, then pembrolizumab if free of recurrence) or observation until a September 2020 amendment allocated all to intervention. Of 208 registered, 185 had tumour sequenced, 171 (92.4 percent) had trackable mutations and 161 entered surveillance. ctDNA was detected by 12 months in 27.3 percent (44 of 161, 95 percent confidence interval 20.6 to 34.9); seven patients relapsed without prior detection. Of 32 allocated to intervention, 72 percent (23) had metastases on staging at ctDNA detection and four declined pembrolizumab; none of the five who started it achieved sustained ctDNA clearance.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Tags: tnbc-evidence
- Journal: Annals of Oncology
- Year: 2023
- DOI: 10.1016/j.annonc.2022.11.005
- Authors: Turner NC, Swift C, Jenkins B, et al.
- Findings: ctDNA detected by 12 months in 27.3 percent (44 of 161; 95 percent CI 20.6 to 34.9); 7 relapses without prior detection.; 72 percent (23 of 32) of ctDNA-positive patients allocated to intervention already had metastases on staging.; None of 5 patients who started pembrolizumab achieved sustained ctDNA clearance.
- What it means: The first prospective test of acting on ctDNA in triple-negative disease, and a negative one: with a quarterly, single-mutation assay the window between detectable DNA and visible metastasis was too short to intervene. Later designs use tumour-informed assays, earlier sampling and drugs with more single-agent activity.
- Caveats: Digital PCR tracking one or two mutations is less sensitive than current tumour-informed panels.; Pembrolizumab alone was the intervention; only five patients received it.

## Sources

- Ann Oncol 2023: https://doi.org/10.1016/j.annonc.2022.11.005
- PubMed: https://pubmed.ncbi.nlm.nih.gov/36423745/
- ClinicalTrials.gov NCT03145961: https://clinicaltrials.gov/study/NCT03145961

## Connected records

- roadmaps: [ctDNA tests roadmap: from a curiosity in plasma to blood tests that decide treatment](https://onco.cc/roadmaps/ctdna-tests/), [Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem](https://onco.cc/roadmaps/tnbc-roadmap/)
- key papers: [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](https://onco.cc/key-papers/paper-radovich-ctdna-ctc-bre12-158-jama-oncol-2020/)
- biomarkers: [ctDNA MRD positivity (molecular residual disease after curative treatment)](https://onco.cc/biomarkers/ctdna-mrd-positive/)
- cancers: [Early triple-negative breast cancer](https://onco.cc/cancers/tnbc-early/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- technologies: [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/), [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/), [MRD / molecular residual disease testing](https://onco.cc/technologies/mrd-testing/)
- drugs: [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/)
- institutions: [Cancer Research UK](https://onco.cc/institutions/cruk/), [The Institute of Cancer Research](https://onco.cc/institutions/icr-london/), [The Royal Marsden](https://onco.cc/institutions/royal-marsden/)
- terms: [Circulating tumour DNA (ctDNA)](https://onco.cc/terms/ctdna/), [Minimal / molecular residual disease (MRD)](https://onco.cc/terms/mrd/), [Residual cancer burden (RCB)](https://onco.cc/terms/rcb/)
- people: [Nicholas Turner](https://onco.cc/people/nicholas-turner/)
- bottlenecks: [Dormant cells and minimal residual disease](https://onco.cc/bottlenecks/b-dormancy-mrd/), [Trial design, endpoints and cost](https://onco.cc/bottlenecks/b-trial-design/)
- journals: [Annals of Oncology](https://onco.cc/journals/annals-of-oncology/)
- ideas: [ctDNA-guided adjuvant decisions after residual disease: escalate the positive, spare the negative](https://onco.cc/ideas/idea-tnbc-ctdna-guided-adjuvant-decisions/)

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