Evidence map›Paper›PMID 40349094›Full record

ArticleCardio-oncology (London, England)2025

Methylation-based biological age and cardiotoxicity risk in breast cancer patients treated with trastuzumab.

Jamila Mammadova, Alicia Richards, Adriana Gonzalez-Torriente, Evan R Adler, Rachel J Cruz, Stefanie Palfi, Dae Hyun Lee, Christine Sam, Mohammed Al-Jumayli, Anders Berglund and 3 more

Abstract read
In one paragraph

Article in Cardio-oncology (London, England), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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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

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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

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

13 authors.

Jamila MammadovaDepartment of Internal Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Alicia RichardsDepartment of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Adriana Gonzalez-TorrienteDepartment of Pediatrics, University of Miami/Jackson Health Systems, Miami, FL, USA.
Evan R AdlerDepartment of Internal Medicine, University of Virginia, Charlottesville, VA, USA.
Rachel J CruzDepartment of Internal Medicine, University of Virginia, Charlottesville, VA, USA.
Stefanie PalfiDivision of Cardiovascular Sciences, Morsani College of Medicine, University of South Florida, Tampa, USA.
Dae Hyun LeeDivision of Cardiovascular Sciences, Morsani College of Medicine, University of South Florida, Tampa, USA.
Christine SamDepartment of Individualized Cancer Management/Senior Adult Oncology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Mohammed Al-JumayliDepartment of Individualized Cancer Management/Senior Adult Oncology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Anders BerglundDepartment of Quantitative Health Sciences, Division of Computational Biology, Mayo Clinic, Jacksonville, FL, USA.
Jong Y ParkDepartment of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Mohammed AlomarDivision of Cardiovascular Sciences, Morsani College of Medicine, University of South Florida, Tampa, USA.
Jacob K KresovichDepartment of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. jacob.kresovich@moffitt.org.

Funding

TRANSLATIONAL RESEARCHP30CA076292 · NCI · UNIVERSITY OF SOUTH FLORIDA · PI John L. Cleveland · 1998 to 2026
$93.5M
NCI NIH HHS P30 CA076292
6 · The paper itself

Abstract

backgroundTrastuzumab is an effective treatment for HER2-positive cancers that has known cardiotoxic properties. Discovering biomarkers that assess cardiotoxicity risk before trastuzumab therapy is essential for protecting the cardiovascular health of cancer patients.

objectiveTo examine the associations between pre-treatment epigenetic age acceleration, circulating leukocyte composition, and candidate single nucleotide polymorphisms (SNPs) with cardiotoxicity risk in breast cancer patients receiving trastuzumab.

methodsAmong a retrospective cohort of HER2-positive breast cancer patients treated with trastuzumab at Moffitt Cancer Center, we profiled blood DNA methylation and genetic profiles. Epigenetic clocks and circulating leukocyte subsets were derived from MethylationEPIC BeadChip data, and candidate SNPs were measured using the Global Screening Array. Cardiotoxicity events (i.e., reductions in left ventricular ejection fraction, symptomatic heart failure), were identified in medical records. Logistic regression models, adjusted for traditional risk factors, estimated odds ratios (ORs) for biomarker associations with cardiotoxicity risk.

resultsAmong 157 patients selected for this study, 39 (25%) experienced cardiotoxicities within one year of treatment initiation. rs776746 was inversely associated with cardiotoxicity risk (OR: 0.38, 95% CI: 0.14, 1.00, P = 0.05). After adjusting for traditional risk factors and leukocyte composition, the Hannum AgeAccel, Horvath AgeAccel, and Horvath Skin and Blood AgeAccel metrics were significantly positively associated with cardiotoxicity risk (ORs ranging between 1.62 and 1.89). Adding Horvath Skin and Blood AgeAccel to traditional cardiotoxicity risk factors significantly improved cardiotoxicity risk prediction (AUC: 0.75 vs. 0.79; P-diff = 0.04).

conclusionsPre-treatment epigenetic age acceleration appears to be a novel biomarker for cardiotoxicity risk that improves cardiotoxicity risk prediction.

Indexed as

Biological ageBreast cancerCardiotoxicityEpigenetic clocksTrastuzumab

Identifiers

PMID40349094
PMCPMC12065287

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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.