- Design
- Systematic review and meta-analysis of prognostic studies
- Population
- 64 studies of patients with advanced breast cancer
- Primary outcome
- Association of ctDNA with PFS and OS
- Effect
- Baseline ctDNA: PFS HR 2.0 (1.8–2.3), OS HR 2.6 (2.1–3.3); unfavourable change PFS HR 2.5 (1.9–3.4)
A meta-analysis in Breast Cancer Research and Treatment (28 September) pooled 64 studies of circulating tumour DNA in advanced breast cancer.
Raised baseline ctDNA was associated with shorter progression-free survival (HR 2.0, 95% CI 1.8 to 2.3; 2,586 patients) and overall survival (HR 2.6, 2.1 to 3.3). An unfavourable change on treatment — ctDNA rising or failing to fall — was associated with shorter progression-free (HR 2.5) and overall survival (HR 2.4), though the overall survival estimate came from only 154 patients. Specific mutations detected at baseline carried worse prognosis, but not consistently.
This establishes ctDNA as a prognostic marker in advanced disease. It does not show that switching treatment on a ctDNA rise, before imaging progression, improves outcomes; trials testing that are under way. For now ctDNA's established clinical use in advanced breast cancer is to detect actionable mutations, and quantitative tracking remains investigational.
- Raised baseline ctDNA marks higher-risk advanced breast cancer.
- A ctDNA rise on treatment was linked to earlier progression, but switching on ctDNA alone is not proven.
- Use ctDNA for actionable mutation testing where indicated.
- Continue to base treatment changes on clinical and imaging progression.
Why it matters
It strengthens the case for ctDNA monitoring trials but not yet for acting on levels in clinic.
Don't overread it
Prognostic value is not the same as evidence that acting on ctDNA improves survival.
The statistics, in plain English
A hazard ratio of 2.0 means progression happened at about twice the rate in patients with raised ctDNA. These are prognostic associations; they say who does worse, not whether a different treatment would help.
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