Prospective circulating tumour DNA surveillance in patients with early high-risk hormone receptor positive, HER2-negative breast cancer in the TRAK-ER study.

Authors

N Cunningham, C Swift, R J Cutts, K Thomas, S Sardo Infirri, F Dalenc, F Le Du, I R Macpherson, C O'Brien, C Palmieri, P Schmid, F Legrand, J Lemonnier, R D Daber, J Zhao, E Gauthier, Afc Okines, D Lee, I Garcia-Murillas, M Robert, F Andre, N C Turner

Published in

Annals of oncology : official journal of the European Society for Medical Oncology. Oct 27, 2026. Epub Oct 27, 2026.

Abstract

CtDNA detection during adjuvant endocrine therapy (ET) strongly associates with recurrence in oestrogen receptor (ER) positive early breast cancer (EBC), with potential to direct switches in adjuvant treatment.
TRAK-ER is a multicentre study for patients with high-risk, ER-positive, HER2-negative EBC, who undergo 3 monthly ctDNA surveillance for up to 3 years during adjuvant ET. High-risk included ≥4 involved lymph nodes; tumour >5 cm; 1-3 involved lymph nodes with additional high-risk features. Upon ctDNA detection, patients have staging scans and in the absence of radiological recurrence, are randomised to receive palbociclib plus fulvestrant or standard ET. ctDNA analysis was performed using a tumour informed assay (Labcorp). We report a protocol-specified analysis of ctDNA detection during surveillance, and results of contemporaneous radiological recurrence.
1133 patients were registered by September 2025, 928 had panels designed (design failed in 16.1% (178/1106), and 912 started ctDNA surveillance including results from 5810 tests (median 7 per patient). ctDNA detection rate was 5.0% (45/897) in the first test, and 1.3% (66/4913) in subsequent tests (P<0.001). Patient level detection rate was 12.0% (109/912), with 1.1% (10/912) of patients having a clinical recurrence without prior ctDNA detection. Detection positively associated with nodal burden (P<0.001) and grade (P=0.04) and negatively associated with increasing time from surgery (P=0.01). Estimated cumulative ctDNA detection rate at 5 years post-surgery was 23.7% (95%CI 14.5-31.9%). In patients with ctDNA detected on the first test, 65.9% (29/44) had radiological recurrence compared to 26.6% (17/64) in patients first detected on subsequent tests (P<0.001).
Results from TRAK-ER inform implementation of ctDNA surveillance in ER-positive EBC, including molecular relapse rates, factors associating with ctDNA detection and contemporaneous radiological recurrence. Ultrasensitive assays detecting ctDNA at low levels, are required to robustly identify patients prior to clinical recurrence. TRAK-ER is ongoing to assess the impact of treatment after molecular relapse detection.

PMID:
42946309
Bibliographic data and abstract were imported from PubMed on 28 Oct 2026.

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