Evidence map›Paper›PMID 42243127›Full record

ArticleNature communications2026

Methylation-based ctDNA monitoring in metastatic breast cancer during CDK4/6 inhibitor therapy.

Mitchell J Elliott, Jesús Fuentes-Antrás, Sasha C Main, Aaron Dou, Elizabeth Shah, Caroline Weipert, Geethika Yalamanchili, Taylor Bird, June Roh, Celeste Yu and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Mitchell J Elliott *Division of Medical Oncology & Hematology, Department of Medicine, Princess Margaret Cancer Centre and University of Toronto, Toronto, ON, Canada.ORCID http://orcid.org/0000-0001-6711-7287
Jesús Fuentes-Antrás *Division of Medical Oncology & Hematology, Department of Medicine, Princess Margaret Cancer Centre and University of Toronto, Toronto, ON, Canada.
Sasha C MainDepartment of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
Aaron DouDivision of Medical Oncology & Hematology, Department of Medicine, Princess Margaret Cancer Centre and University of Toronto, Toronto, ON, Canada.ORCID http://orcid.org/0009-0007-8293-2635
Elizabeth ShahCancer Genomics Program, Princess Margaret Cancer Centre, Toronto, ON, Canada.
Caroline WeipertGuardant Health Inc., Redwood City, CA, USA.
Geethika YalamanchiliGuardant Health Inc., Redwood City, CA, USA.
Taylor BirdDivision of Medical Oncology & Hematology, Department of Medicine, Princess Margaret Cancer Centre and University of Toronto, Toronto, ON, Canada.
June RohDivision of Medical Oncology & Hematology, Department of Medicine, Princess Margaret Cancer Centre and University of Toronto, Toronto, ON, Canada.ORCID http://orcid.org/0009-0000-5832-1702
Celeste YuNEXT Oncology, Hospital Universitario Quirónsalud Madrid, Madrid, Spain.
Michelle B NadlerDivision of Medical Oncology & Hematology, Department of Medicine, Princess Margaret Cancer Centre and University of Toronto, Toronto, ON, Canada.
Eitan AmirDivision of Medical Oncology & Hematology, Department of Medicine, Princess Margaret Cancer Centre and University of Toronto, Toronto, ON, Canada.
Hal K BermanDepartment of Pathology and Laboratory Medicine, University Health Network, Toronto, ON, Canada.ORCID http://orcid.org/0000-0001-7524-7911
Lillian L SiuDivision of Medical Oncology & Hematology, Department of Medicine, Princess Margaret Cancer Centre and University of Toronto, Toronto, ON, Canada.ORCID http://orcid.org/0000-0002-3500-0540
Philippe L BedardDivision of Medical Oncology & Hematology, Department of Medicine, Princess Margaret Cancer Centre and University of Toronto, Toronto, ON, Canada.ORCID http://orcid.org/0000-0002-6771-2999
David W CesconDivision of Medical Oncology & Hematology, Department of Medicine, Princess Margaret Cancer Centre and University of Toronto, Toronto, ON, Canada. dave.cescon@uhn.ca.ORCID http://orcid.org/0000-0002-1080-0998

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Circulating tumor DNA (ctDNA) enables minimally invasive treatment monitoring, yet the clinical validity of longitudinal ctDNA surveillance in metastatic breast cancer remains incompletely defined. Here we show that methylation-based tumor fraction (mTF), a tissue-agnostic epigenomic measure of ctDNA, closely mirrors radiographic response and clinical outcomes in 57 patients with estrogen receptor-positive, HER2-negative metastatic breast cancer receiving endocrine therapy with a CDK4/6 inhibitor across 350 serial plasma timepoints. Baseline ctDNA is detectable in 94.7% of patients. Clearance of mTF on treatment is associated with prolonged time to treatment discontinuation (HR = 0.17, 95% CI: 0.07-0.41; p < 0.0001). A rise in mTF (molecular progression) precedes treatment discontinuation by a median of 5.8 months and outperforms mutation-based tracking, with resistance-associated alterations in ESR1 and RB1 frequently emerging at molecular progression. These findings support prospective evaluation of mTF-guided treatment strategies.

Indexed as

Breast NeoplasmsCirculating Tumor DNACyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6DNA MethylationProtein Kinase InhibitorsErb-b2 Receptor Tyrosine KinasesEstrogen Receptor alphaFemaleHumansMiddle AgedMutationNeoplasm MetastasisRetinoblastoma Binding ProteinsUbiquitin-Protein LigasesCDK4 protein, humanCDK6 protein, humanCirculating Tumor DNACyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6Erb-b2 Receptor Tyrosine KinasesESR1 protein, humanEstrogen Receptor alphaProtein Kinase InhibitorsRB1 protein, humanRetinoblastoma Binding ProteinsUbiquitin-Protein Ligases

Identifiers

PMID42243127
PMCPMC13396465

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.