Treatment strategies for advanced breast cancer (ABC) continue to evolve, but routine clinical decisions and monitoring largely depend on imaging-based assessments. The reviewed meta-analysis evaluated the role of circulating tumour DNA (ctDNA) as a minimally invasive biomarker that could provide near real-time information about tumour burden and treatment response. The authors frame the question around whether ctDNA measures are prognostic for key clinical endpoints, specifically progression-free survival (PFS) and overall survival (OS), in patients with ABC.
The investigators performed a systematic search of Medline, Embase, and the Cochrane databases through 07/02/2025. Eligible studies were those that analysed associations between ctDNA and PFS and/or OS in patients with advanced breast cancer. After screening and eligibility assessment, a total of sixty-four studies were included. The included studies were divided into subgroups for pooled analyses according to the ctDNA measure and outcome assessed.
Study quality was appraised using the Quality in Prognosis Studies (QUIPS) tool. Hazard ratios (HRs) with 95% confidence intervals (CIs) were extracted from eligible reports for meta-analysis. The authors used random-effects models to pool effect estimates across studies, reflecting anticipated heterogeneity among study designs, ctDNA assays, and patient populations.
Pooled data from studies reporting baseline ctDNA levels and PFS included 2,586 patients. The meta-analysis found that elevated ctDNA at baseline was significantly associated with shorter PFS, with a pooled hazard ratio of 2.0 (95% CI: 1.8–2.3). This indicates that, across the included studies and patients, higher baseline ctDNA levels were associated with approximately a twofold increase in the hazard of disease progression or death compared with lower or undetectable baseline ctDNA, as reported by the authors.
For baseline ctDNA and OS, pooled analyses included 2,454 patients. Elevated baseline ctDNA was associated with worse overall survival, with a pooled HR of 2.6 (95% CI: 2.1–3.3). According to the pooled estimate, higher baseline ctDNA correlated with a substantially increased hazard of death across the aggregated study populations.
The authors also assessed prognostic associations for changes in ctDNA over time. Unfavourable changes in ctDNA were linked to poorer outcomes. Specifically, pooled results showed an association between adverse ctDNA dynamics and reduced PFS (n = 710; pooled HR = 2.5; 95% CI: 1.9–3.4). For OS, pooled analysis of studies reporting longitudinal ctDNA change included 154 patients and yielded a pooled HR of 2.4 (95% CI: 1.5–3.8). These findings indicate consistent associations across studies between rising or unfavourable ctDNA trajectories and higher hazards for progression and death.
The provided source text contains abstract-level data and key pooled estimates, but the full article text and some detailed results were not available in the excerpt supplied. The abstract truncates mid-sentence, so additional reported analyses, subgroup findings, assay types, timing of sampling, heterogeneity metrics, sensitivity analyses, and any authors’ recommendations or numerical details beyond those cited cannot be reported here because they were not present in the provided source. Where the source did not report full methodological specifics or complete results in the excerpt, those details are explicitly not available for inclusion.
Based on the pooled analyses reported in the source abstract, elevated ctDNA—measured at baseline or as unfavourable longitudinal changes—is associated with significantly shorter PFS and OS in patients with advanced breast cancer. The pooled hazard ratios indicate roughly twofold or greater increases in hazard for both progression and death when ctDNA is elevated or worsening. The authors assessed study quality using QUIPS and used random-effects meta-analysis to synthesise results from 64 studies, suggesting robustness to between-study variation. The reported findings support the potential clinical relevance of ctDNA for prognostication and monitoring in ABC; however, practitioners and guideline panels should consult the full article for detailed methods, subgroup analyses, and consideration of assay-specific performance before translating these pooled associations into practice.
This systematic review and meta-analysis of sixty-four studies found that elevated baseline ctDNA and unfavourable changes in ctDNA over time are associated with shorter progression-free survival and overall survival in patients with advanced breast cancer. The provided abstract reports pooled hazard ratios supporting these associations, but additional methodological and result-level details from the full text were not available in the supplied source excerpt.