Early use of ctDNA testing can identify likelihood of relapse in TNBC

In the phase 2, proof-of-principle c-TRACK-TN trial circulating tumour DNA (ctDNA) surveillance was used in moderate or high-risk triple-negative breast cancer (TNBC) patients to start additional treatment with pembrolizumab.

A substantial part of patients presenting with TNBC relapse after primary treatment. In previous retrospective findings, ctDNA detection was highly predictive for relapse in patients with TNBC who completed their primary treatment [1,2]. The prospective, multicentre, phase 2 c-TRAK-TN trial (NCT03145961) piloted the prospective use of ctDNA assays in patients treated for early-stage TNBC who were at moderate or high-risk of relapse. Prof. Nicholas Turner (The Institute of Cancer Research, UK) presented primary results of c-TRAK-TN [3].

A total of 208 patients with trackable mutations who completed surgery and adjuvant chemotherapy underwent ctDNA testing at baseline. From these, 161 patients entered ctDNA surveillance every 3 months for 1 year. Patients who were ctDNA-positive were randomised between observation (e.g., standard follow-up) or intervention. In the intervention arm, patients underwent staging scans, and those without metastatic disease were offered pembrolizumab for a year. At 12 months, 27.3% of patients were ctDNA-positive. Patients in the high-risk group were much more likely to be positive for ctDNA at 12 months than those at moderate risk: 55.7% versus 11.8%. Seven patients relapsed without prior ctDNA detection.

Of the ctDNA-positive patients, 14 were assigned to observation and 32 were assigned to intervention. The rate of overt metastatic disease at time of ctDNA detection was 71.9% (23/32), substantially higher than expected. Nine patients were ctDNA-positive without metastatic disease and were offered pembrolizumab; 5 of them started treatment with pembrolizumab. None of these 5 patients exhibited ctDNA clearance after 6 months on pembrolizumab; 1 patient had sustained ctDNA suppression. For the 14 patients assigned to observation, lead time to relapse was a median 4.1 months. Four patients in the observation group remain recurrence-free. All became ctDNA negative after an initial ctDNA-positive result, although 2 have become ctDNA positive again. The 6-month recurrence-free survival rate with ctDNA clearance was 21.4%.

“Our findings have implications for future trial design, most importantly, to start ctDNA testing early and employ more sensitive ctDNA assays that track multiple variants,” concluded Dr Turner. “Potentially, more frequent testing is advisable in the 0–6-month time points, given the rapidity of disease evolution.”

1. Coombes RC, et al. Clin Cancer Res. 2019;25:4255–4263.


2. Garcia-Murillas I, et al. JAMA Oncol. 2019;5:1473–1478.


3. Turner N, et al. Primary results of the cTRAK TN trial: A clinical trial utilising ctDNA mutation tracking to detect minimal residual disease and trigger intervention in patients with moderate and high risk early-stage triple negative breast cancer. GS3-06, SABCS 2021 Virtual Meeting, 7–10 December.

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Posted on 31 January, 2022