Evidence map›Paper›PMID 40288580›Full record

Trial reportThe American journal of clinical nutrition2025

Randomized dose-response trial of n-3 fatty acids in hormone receptor negative breast cancer survivors - impact on breast adipose oxylipin and DNA methylation patterns.

David E Frankhouser, Todd DeWees, Isabel F Snodgrass, Rachel M Cole, Sarah Steck, Danielle Thomas, Chidimma Kalu, Martha A Belury, Steven K Clinton, John W Newman and 1 more

Registry-linked trialAbstract readRandomized Controlled Trial
In one paragraph

Trial report in The American journal of clinical nutrition, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02295059 (Omega-3 Fatty Acids and ERPR), which is not on this map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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.

NCT02295059 naactive not recruitingnot on this map

Omega-3 Fatty Acids and ERPR(-) and HER-2/Neu(+/-) Breast Cancer Prevention

TypeinterventionalSponsorCity of Hope Medical CenterRan2017 to 2027Enrolled80ConditionsBreast CancerArmsomega 3 fatty acids
3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Lipid metabolism in homeostasis and disease.Signal transduction and targeted therapy · 2026
    Review
  3. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

David E FrankhouserDepartment of Computational and Quantitative Medicine, City of Hope, Duarte, CA.
Todd DeWeesDepartment of Computational and Quantitative Medicine, City of Hope, Duarte, CA; Department of Surgery, City of Hope, Duarte, CA.
Isabel F SnodgrassUniversity of California Davis West Coast Metabolomics Center, Genome Center, University of California Davis, Davis, CA.
Rachel M ColeDepartment of Food Science and Technology, The Ohio State University, Columbus, OH.
Sarah SteckThe Ohio State University Comprehensive Cancer Center, Columbus, OH.
Danielle ThomasDepartment of Surgery, City of Hope, Duarte, CA.
Chidimma KaluDepartment of Surgery, City of Hope, Duarte, CA.
Martha A BeluryDepartment of Food Science and Technology, The Ohio State University, Columbus, OH; The Ohio State University Comprehensive Cancer Center, Columbus, OH.
Steven K ClintonThe Ohio State University Comprehensive Cancer Center, Columbus, OH; Department of Internal Medicine, The Ohio State University, Columbus, OH.
John W NewmanUniversity of California Davis West Coast Metabolomics Center, Genome Center, University of California Davis, Davis, CA; Department of Nutrition, University of California Davis, Davis, CA; United States Department of Agriculture Agricultural Research Service, Western Human Nutrition Research Center, Davis, CA.
Lisa D YeeDepartment of Surgery, City of Hope, Duarte, CA; City of Hope Comprehensive Cancer Center, Duarte, CA. Electronic address: lyee@coh.org.

Funding

Translational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI Soledad A Fernandez · 1985 to 2026
$132.3M
Transgenic Mouse FacilityP30CA033572 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI John Charles Williams · 1985 to 2026
$86.3M
Cancer Metabolism Training ProgramT32CA221709 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI David K. Ann, Victoria L. Seewaldt · 2018 to 2026
$1.8M
Omega-3 fatty acids and ERPR(-) and HER-2/neu(+) breast cancer preventionR01CA164019 · NCI · OHIO STATE UNIVERSITY · PI YEE, LISA D · 2014 to 2018
$1.3M
NCI NIH HHS P30 CA016058NCI NIH HHS P30 CA033572NCI NIH HHS R01 CA164019NCI NIH HHS T32 CA221709
6 · The paper itself

Abstract

backgroundIncreasing evidence suggests the unique susceptibility of estrogen receptor and progesterone receptor negative [ERPR(-)] breast cancer to dietary fat amount and type. Dietary n-3 (ω-3) polyunsaturated fatty acids (PUFAs), such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), may modulate breast adipose fatty acids and downstream metabolites to counteract procarcinogenic signaling in the mammary microenvironment.

objectivesWe aimed to determine effects of ∼1 to 5 g/d EPA+DHA over 12 mo on breast adipose fatty acid and oxylipin profiles in survivors of ERPR(-) breast cancer, a high-risk molecular subtype.

methodsWe conducted a proof-of-concept 12-mo randomized double-blind trial comparing ∼5 g/d and ∼1 g/d EPA+DHA supplementation in females within 5 y of completing standard therapy for ERPR(-) breast cancer Stages 0 to III. Blood and breast adipose tissue specimens were collected every 3 mo for fatty acid, oxylipin, and DNA methylation (DNAm) analyses.

resultsA total of 51 participants completed the 12-mo intervention. Study treatments were generally well tolerated. Although both doses increased n-3 PUFAs from baseline in breast adipose, erythrocytes, and plasma, the 5 g/d supplement was more potent with differences (% total fatty acids) of 0.76 (95% confidence interval [CI]: 0.56, 0.96), 6.25 (95% CI: 5.02, 7.48), and 5.89 (95% CI: 4.53, 7.25), respectively. The 5 g/d dose also reduced plasma triglycerides from baseline, with changes (mg/dL) of 27.38 (95% CI: 10.99, 43.78) and 24.58 (95% CI: 9.05, 40.10) at 6 and 12 months, respectively. Breast adipose oxylipins showed dose-dependent increases in DHA and EPA metabolites. Distinct DNAm patterns in adipose tissue after 12 mo suggest potential downregulation of aberrant lipid metabolism pathways at the 5 g/d dose.

conclusionsOver 1 y, EPA+DHA dose-dependently increased breast adipose concentrations of these fatty acids and their derivative oxylipin metabolites and produced differential DNAm profiles involved in metabolism-related pathways critical to ERPR(-) breast cancer development. This distinct metabolic and epigenetic modulation of the breast microenvironment is achievable with high-dose n-3 PUFA supplementation. This trial was registered at clinicaltrials.gov as NCT02295059.

Indexed as

Adipose TissueBreastBreast NeoplasmsDNA MethylationFatty Acids, Omega-3OxylipinsAdultAgedCancer SurvivorsDietary SupplementsDocosahexaenoic AcidsDose-Response Relationship, DrugDouble-Blind MethodEicosapentaenoic AcidFemaleHumansDocosahexaenoic AcidsEicosapentaenoic AcidFatty Acids, Omega-3OxylipinsReceptors, EstrogenReceptors, Progesteronebreast adipose DNA methylationbreast adipose oxylipinsbreast cancerdose-responsen–3 PUFAsrandomized clinical trial

Identifiers

PMID40288580
PMCPMC12308080

What Socratic holds

Textmetadata
Read underepoch 390

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 Socratic graph.