Evidence map›Paper›PMID 26169690›Full record

ArticleNature communications2015

DNA methylation of oestrogen-regulated enhancers defines endocrine sensitivity in breast cancer.

Andrew Stone, Elena Zotenko, Warwick J Locke, Darren Korbie, Ewan K A Millar, Ruth Pidsley, Clare Stirzaker, Peter Graham, Matt Trau, Elizabeth A Musgrove and 3 more

Registry-linked trialOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05814224 (Monitoring luminAl Breast Cancer Through the Evaluation of Mutational and epiGeNEtic alteraTIons of Circulating ESR1 DNA), which is not on this map. Cited by 86 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
86citing papers in PubMed, 1 pooled it
5.9field-weighted citation impact, top 3% of its field
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.

NCT05814224 naunknown statusnot on this mapstarted 2018, after this paper: background citation

Monitoring luminAl Breast Cancer Through the Evaluation of Mutational and epiGeNEtic alteraTIons of Circulating ESR1 DNA

TypeinterventionalSponsorCentro di Riferimento Oncologico - AvianoRan2018 to 2024Enrolled164ConditionsHormone Receptor Positive Breast Carcinoma, Breast Neoplasms, Neoplasms, Breast, Breast DiseasesArmsLiquid biopsy and CT scan
3 · Its place in the literature

Who cites it

86 citing papers in PubMed, 1 synthesis or guideline pooled it, 133 citations in OpenAlex.

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  13. Association of Intergenic and IntragenicInternational journal of molecular sciences · 2025
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26 more citing papers are in PubMed but not listed here.

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

13 authors at 5 institutions in 2 countries.

Andrew Stone1] Epigenetics Research Program, Genomics and Epigenetics Division, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia [2] Faculty of Medicine, St Vincent's Clinical School, UNSW, NSW 2052 &St Vincent's Hospital, Sydney, New South Wales 2010, Australia.
Elena Zotenko1] Epigenetics Research Program, Genomics and Epigenetics Division, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia [2] Faculty of Medicine, St Vincent's Clinical School, UNSW, NSW 2052 &St Vincent's Hospital, Sydney, New South Wales 2010, Australia.
Warwick J Locke1] Epigenetics Research Program, Genomics and Epigenetics Division, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia [2] Faculty of Medicine, St Vincent's Clinical School, UNSW, NSW 2052 &St Vincent's Hospital, Sydney, New South Wales 2010, Australia.
Darren KorbieAustralian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Queensland 4072, Australia.
Ewan K A Millar1] Translational Breast Cancer Research, The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia [2] Department of Anatomical Pathology, South Eastern Area Laboratory Service, St George Hospital, Kogarah, Sydney, New South Wales 2217, Australia [3] School of Medicine and Health Sciences, University of Western Sydney, Campbelltown, Sydney, New South Wales 2560, Australia [4] Faculty of Medicine, UNSW, Kensington, New South Wales 2052, Australia.
Ruth Pidsley1] Epigenetics Research Program, Genomics and Epigenetics Division, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia [2] Faculty of Medicine, St Vincent's Clinical School, UNSW, NSW 2052 &St Vincent's Hospital, Sydney, New South Wales 2010, Australia.
Clare Stirzaker1] Epigenetics Research Program, Genomics and Epigenetics Division, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia [2] Faculty of Medicine, St Vincent's Clinical School, UNSW, NSW 2052 &St Vincent's Hospital, Sydney, New South Wales 2010, Australia.
Peter Graham1] Faculty of Medicine, UNSW, Kensington, New South Wales 2052, Australia [2] Department of Radiation Oncology, Cancer Care Centre, St George Hospital, Kogarah, Sydney, New South Wales 2217, Australia.
Matt TrauAustralian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Queensland 4072, Australia.
Elizabeth A Musgrove1] Faculty of Medicine, St Vincent's Clinical School, UNSW, NSW 2052 &St Vincent's Hospital, Sydney, New South Wales 2010, Australia [2] Translational Breast Cancer Research, The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia [3] Wolfson Wohl Cancer Research Centre, University of Glasgow, Glasgow G61 1BD, UK.
Robert I NicholsonBreast Cancer Molecular Pharmacology Group, School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Wales CF10 3NB, UK.
Julia M W GeeBreast Cancer Molecular Pharmacology Group, School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Wales CF10 3NB, UK.
Susan J Clark1] Epigenetics Research Program, Genomics and Epigenetics Division, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia [2] Faculty of Medicine, St Vincent's Clinical School, UNSW, NSW 2052 &St Vincent's Hospital, Sydney, New South Wales 2010, Australia.
Garvan Institute of Medical Research · AUSt Vincent's Clinic · AUCardiff University · GBUniversity of Queensland · AUUNSW Sydney · AU

Funding

Cancer Research UK C596/A18076
6 · The paper itself

Abstract

Expression of oestrogen receptor (ESR1) determines whether a breast cancer patient receives endocrine therapy, but does not guarantee patient response. The molecular factors that define endocrine response in ESR1-positive breast cancer patients remain poorly understood. Here we characterize the DNA methylome of endocrine sensitivity and demonstrate the potential impact of differential DNA methylation on endocrine response in breast cancer. We show that DNA hypermethylation occurs predominantly at oestrogen-responsive enhancers and is associated with reduced ESR1 binding and decreased gene expression of key regulators of ESR1 activity, thus providing a novel mechanism by which endocrine response is abated in ESR1-positive breast cancers. Conversely, we delineate that ESR1-responsive enhancer hypomethylation is critical in transition from normal mammary epithelial cells to endocrine-responsive ESR1-positive cancer. Cumulatively, these novel insights highlight the potential of ESR1-responsive enhancer methylation to both predict ESR1-positive disease and stratify ESR1-positive breast cancer patients as responders to endocrine therapy.

Indexed as

AdultAgedAntineoplastic Agents, HormonalBreast NeoplasmsCarcinoma, Ductal, BreastCarcinoma, LobularChromatin ImmunoprecipitationDNA MethylationDrug Resistance, NeoplasmEnhancer Elements, GeneticEstrogen Receptor alphaFemaleHumansMCF-7 CellsMiddle AgedMultiplex Polymerase Chain ReactionAntineoplastic Agents, HormonalESR1 protein, humanEstrogen Receptor alphaTamoxifen

Identifiers

PMID26169690
PMCPMC4510968
OpenAlexW1902615984

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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 OpenQuestion graph.