Dynamic circulating tumor DNA profiling of ESR1 mutations in HR+/HER2− advanced breast cancer: from prognostic biomarker to clinical decision-making – a comprehensive review
- Study type
- Review article
- Design
- Comprehensive narrative review following PRISMA guidelines (quantitative meta-analysis was not possible because of clinical and methodological heterogeneity)
- Sample size
- 9 high-quality studies
- Source
- Front. Oncol. · 2026
In plain words
In some people with advanced hormone receptor-positive breast cancer, the tumour develops a change during treatment in a gene called ESR1, which can make hormone therapy stop working. This change can be followed with a blood test (liquid biopsy). This review shows that monitoring these mutations may help the doctor change treatment at the right time, but more studies and standardised testing are still needed before it is used routinely.
Key results
Treatment arms and regimens
CDK4/6 inhibitor plus endocrine therapy; in the SERENA-6 trial, pre-emptive switch to camizestrant after detection of an ESR1 mutation in ctDNA. Dosing details in the full text.
Source of the regimen details: Abstract of the paper
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
Studies were included if they reported ESR1 mutations in ctDNA and clinical outcomes in patients with HR-positive/HER2-negative metastatic/advanced breast cancer treated with a CDK4/6 inhibitor (CDK4/6i) plus endocrine therapy (ET).
Endpoints
The prognostic and predictive value of pre-treatment and on-treatment ESR1 mutations in ctDNA, and their evolution into "dynamic intervention nodes" for precision decision-making.
Safety and side effects
The abstract gives no information on adverse events.
Clinical significance and place in guidelines
According to this review, ESR1 mutations in ctDNA have moved from a prognostic marker to potential clinical decision nodes, and the SERENA-6 findings support pre-emptive treatment switching. The authors stress that routine adoption requires prospective validation, harmonised assay standards and consensus on monitoring protocols. The status of approvals and clinical guidelines should be checked separately.
Limitations
Considerable clinical and methodological heterogeneity across studies precluded quantitative meta-analysis, and only narrative synthesis was possible. Only nine studies were included. Routine clinical use requires prospective validation, harmonised assay standards and consensus on monitoring protocols.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.