ArticleAnnals of oncology : official journal of the European Society for Medical Oncology2025
Prognostic significance of early on-treatment evolution of circulating tumor DNA in advanced ER-positive/HER2-negative breast cancer.
Article in Annals of oncology : official journal of the European Society for Medical Oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Dynamic circulating tumor DNA profiling of ESR1 mutations in HR+/HER2- advanced breast cancer: from prognostic biomarker to clinical decision-making - a comprehensive review.Frontiers in oncology · 2026Pooled it
- HDAC inhibitor tucidinostat and metronomic capecitabine plus endocrine therapy for patients with HR-positive HER2-negative advanced breast cancer after CDK4/6 inhibitors treatment: clinical findings and exploratory circulating tumor cell and ctDNA biomarker analyses of a multicenter, phase 2 study (SYSUCC-020 trial).Signal transduction and targeted therapy · 2026Trial
- Tumor-Informed ddPCR for Personalized Longitudinal ctDNA Monitoring in Advanced Solid Tumors: Molecular-Radiological Concordance and Molecular Lead Time.International journal of molecular sciences · 2026Article
- Assessing the utility of ctDNA as a prognostic marker in advanced ER-positive/HER2-negative breast cancer.Translational cancer research · 2026Article
- Liquid biopsy in solid tumours: expert opinion paper of the European society of pathology.Virchows Archiv : an international journal of pathology · 2026Review
- Comments on "Prognostic Significance of Pretreatment ¹⁸F-FDG PET/CT Parameters in Patients With ER+/HER2- Metastatic Breast Cancer Treated With CDK4/6 Inhibitors Plus Endocrine Therapy".Korean journal of radiology · 2026Article
- Article
- Cyclin-dependent kinase 4 and 6 inhibitors and the breast cancer immune ecosystem: immune remodeling, resistance, and therapeutic reprogramming.Frontiers in immunology · 2026Review
- Multi-scale data reveal a CD24(+) MUCL1(+) tumor subgroup associated with unfavorable prognosis in ER+ breast cancer.Frontiers in immunology · 2025Article
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25 authors.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundPatients with advanced estrogen receptor-positive, HER2-negative breast cancer commonly develop resistance to treatment with hormone therapy and cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. Responders cannot be distinguished from nonresponders after the first cycle of treatment under current practice. We assessed circulating tumor DNA (ctDNA) measures at early timepoints as prognostic markers. PATIENTS AND
methodsPaired plasma samples were collected at baseline and early on-treatment (median 28 days) from 369 patients with advanced ER-positive/HER2-negative breast cancer treated in the PADA-1 trial with hormone therapy and a CDK4/6 inhibitor. Cell-free DNA was profiled with a 497-gene panel (Guardant360 LDT).
resultsBaseline ctDNA levels, including the mean variant allele frequency (VAF) [progression-free survival (PFS) hazard ratio (HR) 1.07, 95% confidence interval (CI) 1.05-1.09), P < 0.001; overall survival (OS) HR 1.08, 95% CI 1.05-1.11, P < 0.001] and the number of driver somatic mutations (PFS HR 1.13, 95% CI 1.07-1.19, P < 0.001; OS HR 1.16, 95% CI 1.07-1.24, P < 0.001) were prognostic. Early on-treatment ctDNA dynamics were also associated with outcomes, including the number of driver somatic mutations with VAF > 0.5% at both timepoints (PFS HR 1.39, 95% CI 1.27-1.53, P < 0.001; OS HR 1.51, 95% CI 1.35-1.68, P < 0.001) and the number of driver somatic mutations with a VAF increase (PFS HR 1.31, 95% CI 1.19-1.44, P < 0.001; OS HR 1.10, 95% CI 1.02-1.18, P = 0.02). A ctDNA-based risk model incorporating baseline and dynamic ctDNA features was independently prognostic from RECIST in multivariable models (test set: OS HR 4.10, 95% CI 1.93-8.72, P < 0.001; PFS HR 1.86, 95% CI 1.16-2.97, P = 0.009). The integration of ctDNA features into a clinical model improved survival discrimination for PFS [C-index 64.7% (± 2.5%) for a ctDNA and clinical model versus 59.3% (± 2.2%) for a clinical-only model, P = 0.027] and for OS [C-index 70.0% (± 3.4%) versus 60.3% (± 4.2%), P = 0.035].
conclusionsEarly on-treatment evolution of ctDNA is prognostic for both PFS and OS in advanced ER-positive/HER2-negative breast cancer. A ctDNA-based risk model improves upon traditional RECIST and clinical parameters, advocating for ctDNA as a prognostic biomarker in clinical practice.
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