Evidence map›Paper›PMID 35751095›Full record

ArticleBreast cancer research : BCR2022

DNA methylation changes in response to neoadjuvant chemotherapy are associated with breast cancer survival.

Christine Aaserød Pedersen, Maria Dung Cao, Thomas Fleischer, Morten B Rye, Stian Knappskog, Hans Petter Eikesdal, Per Eystein Lønning, Jörg Tost, Vessela N Kristensen, May-Britt Tessem and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Breast cancer research : BCR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 1 pooled it
2.5field-weighted citation impact, top 10% 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.

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

28 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.

  1. Pooled it
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  13. Decoding the Epigenome of Breast Cancer.International journal of molecular sciences · 2025
    Review
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  15. Article
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  18. A review on trends in development and translation of omics signatures in cancer.Computational and structural biotechnology journal · 2024
    Review
  19. Circulating methylatedOncology letters · 2024
    Article
  20. Article
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

12 authors at 6 institutions in 2 countries.

Christine Aaserød Pedersen *Department of Circulation and Medical Imaging, NTNU - Norwegian University of Science and Technology, Trondheim, Norway. christine.a.pedersen@ntnu.no.
Maria Dung Cao *Department of Circulation and Medical Imaging, NTNU - Norwegian University of Science and Technology, Trondheim, Norway. maria.d.cao@hiof.no.
Thomas FleischerDepartment of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
Morten B RyeClinic of Surgery, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
Stian KnappskogK.G. Jebsen Centre for Genome-Directed Cancer Therapy, Department of Clinical Science, University of Bergen, Bergen, Norway.
Hans Petter EikesdalK.G. Jebsen Centre for Genome-Directed Cancer Therapy, Department of Clinical Science, University of Bergen, Bergen, Norway.
Per Eystein LønningK.G. Jebsen Centre for Genome-Directed Cancer Therapy, Department of Clinical Science, University of Bergen, Bergen, Norway.
Jörg TostLaboratory for Epigenetics and Environment, Centre National de Recherche en Génomique Humaine, CEA - Institut de Biologie François Jacob, Université Paris Saclay, 91000, Evry, France.
Vessela N KristensenDepartment of Medical Genetics, Institute of Clinical Medicine, Oslo University Hospital, Oslo, Norway.
May-Britt TessemDepartment of Circulation and Medical Imaging, NTNU - Norwegian University of Science and Technology, Trondheim, Norway.
Guro F GiskeødegårdClinic of Surgery, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
Tone F BathenDepartment of Circulation and Medical Imaging, NTNU - Norwegian University of Science and Technology, Trondheim, Norway.
Norwegian University of Science and Technology · NOSt Olav's University Hospital · NOHaukeland University Hospital · NOOslo University Hospital · NOCentre National de Recherche en Génomique Humaine · FRUniversity of Bergen · NO

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundLocally advanced breast cancer is a heterogeneous disease with respect to response to neoadjuvant chemotherapy (NACT) and survival. It is currently not possible to accurately predict who will benefit from the specific types of NACT. DNA methylation is an epigenetic mechanism known to play an important role in regulating gene expression and may serve as a biomarker for treatment response and survival. We investigated the potential role of DNA methylation as a prognostic marker for long-term survival (> 5 years) after NACT in breast cancer.

methodsDNA methylation profiles of pre-treatment (n = 55) and post-treatment (n = 75) biopsies from 83 women with locally advanced breast cancer were investigated using the Illumina HumanMethylation450 BeadChip. The patients received neoadjuvant treatment with epirubicin and/or paclitaxel. Linear mixed models were used to associate DNA methylation to treatment response and survival based on clinical response to NACT (partial response or stable disease) and 5-year survival, respectively. LASSO regression was performed to identify a risk score based on the statistically significant methylation sites and Kaplan-Meier curve analysis was used to estimate survival probabilities using ten years of survival follow-up data. The risk score developed in our discovery cohort was validated in an independent validation cohort consisting of paired pre-treatment and post-treatment biopsies from 85 women with locally advanced breast cancer. Patients included in the validation cohort were treated with either doxorubicin or 5-FU and mitomycin NACT.

resultsDNA methylation patterns changed from before to after NACT in 5-year survivors, while no significant changes were observed in non-survivors or related to treatment response. DNA methylation changes included an overall loss of methylation at CpG islands and gain of methylation in non-CpG islands, and these changes affected genes linked to transcription factor activity, cell adhesion and immune functions. A risk score was developed based on four methylation sites which successfully predicted long-term survival in our cohort (p = 0.0034) and in an independent validation cohort (p = 0.049).

conclusionOur results demonstrate that DNA methylation patterns in breast tumors change in response to NACT. These changes in DNA methylation show potential as prognostic biomarkers for breast cancer survival.

Indexed as

Breast NeoplasmsNeoadjuvant TherapyAntineoplastic Combined Chemotherapy ProtocolsChemotherapy, AdjuvantDNA MethylationDoxorubicinFemaleHumansKaplan-Meier EstimatePrognosisDoxorubicinBreast cancerChemotherapyDNA methylationLocally advanced breast cancerNeoadjuvant chemotherapySurvivalTreatment response

Identifiers

PMID35751095
PMCPMC9233373
OpenAlexW4283360345

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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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.