# Biomarkers of oxidative stress, inflammation, and cardiac damage as markers of long-term radiation-induced cardiovascular outcomes in breast cancer

> **NIH NIH R21** · UNIVERSITY OF WASHINGTON · 2020 · $291,393

## Abstract

Background: Survival rates from breast cancer have improved; however, many breast cancer survivors
experience treatment-induced adverse effects including late-onset cardiovascular disease due to radiation
therapy. Radiation-induced cardiovascular disease (RICVD), which can appear 5 – 10 or more years after
radiation, is a substantial cause of increased morbidity and mortality among breast cancer survivors. Currently,
it is not known how to best identify individuals who will develop RICVD, as RICVD often occurs years after
treatment and is often neglected in research due to the expense of following participants long-term. As a result,
the primary body of literature in cardio-oncology examines short-term cardiac outcomes, mainly related to
chemotherapy. Based on these studies, biomarkers of cardiac damage and inflammation have been identified
as acute contributors of cardiotoxicity. While RICVD likely shares some pathways of chemotherapy-induced
CVD, this has not been definitively tested in research studies. Pathways, such as oxidative stress and fibrosis,
are thought to play a large role in the development of RICVD. Purpose: The purpose of this study is to examine
post-treatment serum biomarkers of oxidative stress (8-OH-dG, MPO), fibrosis (TGF-B), cardiac damage (TnI-I,
cystatin-C), and inflammation (IL-6, GDF-15, CRP) in the development of long-term RICVD in breast cancer
survivors treated with radiation and to stratify by right- vs. left-sided radiation. Specifically, we aim to 1) to
examine the risk of RICVD and CVD death in breast cancer survivors treated with radiation (vs. controls)
associated with biomarkers (post-treatment), 2) to examine the risk of RICVD and CVD death (vs. controls)
comparing breast cancer survivors treated with right-sided radiation vs. left-sided radiation, and 3) to examine
the association of post-treatment biomarkers in the risk of RICVD and CVD death (vs. controls) among breast
cancer survivors, stratified by right- vs. left-sided radiation. Methods: We propose a nested, case-control design
within the Women's Health Initiative Life and Longevity After Cancer (WHI LILAC), a national, prospective, cohort
study. Inclusion criteria are: 1) serum sample available at WHI baseline and year 3 and 2) a breast cancer
diagnosis and radiation treatment between the two serum collection time points. All biomarkers will be assessed
at both timepoints using ELISA. Women with an adjudicated heart failure, myocardial infarction, coronary
coronary heart disease, or other cardiovascular death outcome occurring post-breast cancer will constitute the
case group (n = 56) while women without a RICVD outcome will constitute the control group (n = 128). Logistic
regression will be used. Summary: This study leverages the WHI dataset, which is an excellent cohort to address
the identified research gaps, given the availability of biospecimens previously collected from participants with
nearly 20 years of outcome follow-up. This study is signif...

## Key facts

- **NIH application ID:** 9952038
- **Project number:** 1R21HL152149-01
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Kerryn W Reding
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $291,393
- **Award type:** 1
- **Project period:** 2020-07-15 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9952038

## Citation

> US National Institutes of Health, RePORTER application 9952038, Biomarkers of oxidative stress, inflammation, and cardiac damage as markers of long-term radiation-induced cardiovascular outcomes in breast cancer (1R21HL152149-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/9952038. Licensed CC0.

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