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

氧化应激、炎症和心脏损伤的生物标志物作为乳腺癌长期辐射诱发心血管结局的标志物

• 批准号: 10217251
• 负责人: Kerryn W Reding
• 金额: $ 15.8万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-15 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10217251
• 关键词: 8-hydroxy-2' -deoxyguanosine; Acute; Address; Adjuvant Therapy; Adverse effects; Aftercare; Ancillary Study; Attention; Biological Markers; Breast Cancer Patient; Breast Cancer Treatment; Breast Cancer survivor; C-reactive protein; Cancer Survivor; Cancer Survivorship; Cardiac; Cardiotoxicity; Cardiovascular Diseases; Cardiovascular system; Cessation of life; Characteristics; Chronic; Collection; Control Groups; Coronary; Coronary heart disease; Data; Data Set; Detection; Development; Disease; Disease Outcome; Enzyme-Linked Immunosorbent Assay; Event; Exposure to; Fibrosis; Future; GDF15 gene; Handedness; Heart; Heart Valve Diseases; Heart failure; Individual; Inflammation; Interleukin-6; Intervention; Lead; Left; Life; Literature; Logistic Regressions; Longevity; Malignant Neoplasms; Methods; Monitor; Morbidity - disease rate; Myocardial Infarction; Myocardial Ischemia; Myocarditis; National Heart, Lung, and Blood Institute; Nested Case-Control Study; Oncology; Outcome; Oxidative Stress; Participant; Pathway interactions; Patients; Pericardial body location; Peroxidases; Pharmaceutical Preparations; Play; Prospective cohort study; Radiation; Radiation therapy; Research; Risk; Role; Sampling; Serum; Side; Specimen; Survival Rate; Testing; Time; Transforming Growth Factor beta; Translating; Troponin I; United States; Woman; Women' s Health; Work; acute coronary syndrome; adjudicate; adjudication; base; breast cancer diagnosis; cardioprotection; cardiovascular disorder risk; case control; chemotherapy; clinical practice; cohort; design; experience; follow-up; heart damage; high risk; improved; inclusion criteria; malignant breast neoplasm; mortality; neglect; post gamma-globulins; programs; prospective; radiation risk; research study; risk prediction model; risk stratification; targeted biomarker

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 significant as it will investigate biomarkers targeting multiple, relevant pathways potentially associated with RICVD, which could be used in future studies to improve the identification and prediction of RICVD in cancer survivors.

背景：乳腺癌的存活率有所提高；但是，许多乳腺癌幸存者 经验治疗引起的不良反应，包括由于辐射引起的晚发心血管疾病 治疗。辐射诱导的心血管疾病（RICVD），可以在5 - 10或更长时间后出现 辐射是乳腺癌存活中发病率和死亡率增加的次要原因。现在， 尚不知道如何最好地识别将会发展RICVD的个人，因为RICVD经常发生在几年之后 治疗，并且由于长期以下参与者的费用而在研究中经常被忽略。因此， 心脏肿瘤学检查中文献的主要体系短期心脏结局，主要与 化学疗法。基于这些研究，已经确定了心脏损伤和炎症的生物标志物 作为心脏毒性的急性贡献者。虽然RICVD可能具有化学疗法诱导的一些途径 CVD，这在研究研究中尚未得到明确的测试。途径，例如氧化应激和纤维化， 人们认为在RICVD的发展中发挥了重要作用。目的：本研究的目的是检查 治疗后血清氧化物胁迫（8-OH-DG，MPO），纤维化（TGF-B），心脏损伤（TNI-I，，TNI-I， Cystatin-C）和注射（IL-6，GDF-15，CRP）在乳腺癌的长期RICVD中 经过辐射处理的幸存者并通过右侧与左侧辐射进行分层。具体来说，我们的目标是1） 检查用辐射治疗的乳腺癌存活中RICVD和CVD死亡的风险（vs.对照） 与生物标志物（治疗后）相关，2）检查RICVD和CVD死亡的风险（与对照） 比较用右侧辐射与左侧辐射治疗的乳腺癌存活和3）检查 治疗后生物标志物在RICVD和CVD死亡风险（vs.对照中）的关联 癌症存活，由右侧与左侧辐射分层。方法：我们提出了一个嵌套的，案例对照的设计 在癌症之后的妇女健康倡议生命和寿命中（whi lilac），国家，潜在的，同类 学习。纳入标准是：1）在基线和第3年和2）乳腺癌的血清样本 两个血清收集时间点之间的诊断和辐射处理。所有生物标志物将被评估 在两个时间点，都使用ELISA。心力衰竭，心肌梗塞，冠状动脉的女性 冠状动脉疾病或其他心血管死亡结局发生后胸癌将构成 病例组（n = 56），而没有RICVD结果的女性将构成对照组（n = 128）。逻辑 回归将被使用。摘要：这项研究利用了WHI数据集，这是一个很好的人群 鉴于以前从参与者那里收集的生物测量的可用性，已确定的研究差距 近20年的结果随访。这项研究很重要，因为它将研究针对多种的生物标志物 与RICVD相关的相关途径，可以在以后的研究中使用，以改善 癌症存活中RICVD的鉴定和预测。