Circulating tumour DNA and its clinical relevance in predicting progression-free survival and overall survival in patients with advanced breast cancer: a systematic review and meta-analysis.

Authors

Cæcilie Ottosen, Ea Kragelund, Mette Abildgaard Pedersen, Vivi Quoc Nguyen, Sakina Kousgaard Khan, Helene Borup Larsen, Anders Lerche Møller, Sofie Høier Gamborg-Kvist, Karen-Lise Garm Spindler, Anne Sofie Brems-Eskildsen, Louise Bach Callesen

Published in

Breast cancer research and treatment. Volume 219. Issue 3. Sep 28, 2026. Epub Sep 28, 2026.

Abstract

Treatment strategies for advanced breast cancer (ABC) are rapidly evolving, but treatment decisions and monitoring remain dependent on imaging-based assessments. Circulating tumour DNA (ctDNA) has emerged as a minimally invasive biomarker with potential to provide real-time assessments, yet its clinical relevance in ABC has not been established. This systematic review and meta-analysis evaluates the prognostic value of ctDNA in ABC.
Medline, Embase, and Cochrane databases were systematically searched up to 07/02/2025. Eligible studies analysed associations between ctDNA and progression free survival (PFS) and/or overall survival (OS) in patient with ABC. Study quality was assessed using the Quality in Prognosis Studies Tool. Hazard ratios (HR) with 95% confidence intervals (CI) were extracted, and meta-analyses were performed using random-effects models.
Sixty-four studies were included and divided into subgroups. Elevated ctDNA levels at baseline were significantly associated with shorter PFS (n = 2,586, pooled HR = 2.0; 95% CI: 1.8-2.3) and OS (n = 2,454, pooled HR = 2.6; 95% CI: 2.1-3.3). Unfavourable changes in ctDNA levels were associated with reduced PFS (n = 710, pooled HR = 2.5; 95% CI: 1.9-3.4) and OS (n = 154, pooled HR = 2.4; 95% CI: 1.5-3.8). Additionally, analyses on specific genetic alterations in ctDNA and survival outcomes indicated a less favourable prognosis when detected at baseline. However, results were not consistent.
This review supports an association between baseline ctDNA levels, on-treatment changes in ctDNA levels, and survival outcomes in ABC. Furthermore, specific genetic alterations in ctDNA add prognostic information and may support treatment tailoring.
Registered in PROSPERO (CRD42024534851).

PMID:
42804029
Bibliographic data and abstract were imported from PubMed on 29 Sep 2026.

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