Biomarkers of Long-Term Fatigue in Breast Cancer Survivors Treated with Radiation

接受放射治疗的乳腺癌幸存者长期疲劳的生物标志物

• 批准号: 9758471
• 负责人: Alexi L Vasbinder
• 金额: $ 4.41万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-06-16 至 2021-06-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9758471
• 关键词: 8-hydroxy-2' -deoxyguanosine; Activities of Daily Living; Acute; Affect; Aftercare; Automobile Driving; Behavior Therapy; Biological; Biological Markers; Breast; Breast Cancer Patient; Breast Cancer survivor; C-reactive protein; Cancer Survivor; Cancer Survivorship; Cardiotoxicity; Collection; Data; Development; Diagnosis; EFRAC; Enrollment; Enzyme-Linked Immunosorbent Assay; Exposure to; Failure; Fatigue; Fellowship; Future; Goals; Heart; Heart failure; Individual National Research Service Award; Inflammation; Inflammatory; Interleukin-6; Intervention; Lead; Left; Life; Link; Logistic Regressions; Long-Term Survivors; Longevity; Malignant Neoplasms; Measures; Mediating; Mediation; Mental Depression; Methods; Modeling; Nursing Research; Outcome; Oxidative Stress; Pathway interactions; Patients; Physiological; Population; Positioning Attribute; Postdoctoral Fellow; Prevention; Quality of life; Radiation; Radiation exposure; Radiation therapy; Reporting; Research; Research Personnel; Research Support; Research Training; Risk; Role; SF-36; Sampling; Serum; Side; Specimen; Survival Rate; Survivors; Symptoms; Testing; Time; Training; Translational Research; Treatment Protocols; United States; United States National Institutes of Health; Universities; Washington; Woman; Women' s Health; biobehavior; breast cancer diagnosis; cancer therapy; cardiorespiratory fitness; case control; cohort; design; doctoral student; exercise intolerance; experience; follow-up; heart damage; heart function; improved; inflammatory marker; insight; malignant breast neoplasm; mortality; personalized approach; post gamma-globulins; pre-doctoral; predictive modeling; preservation; prevent; programs; prospective; radiation effect; reduce symptoms; sample collection; symptom science; targeted biomarker; therapy development

PROJECT SUMMARY The purpose of this Ruth L. Kirschstein National Research Service Award (NRSA) Individual Pre-Doctoral Fellowship in Nursing Research (F31) application is to provide research training for Ms. Vasbinder, a second year doctoral student at the University of Washington, and prepare her for a post-doctoral position. The long- term goal of this training is for this applicant to develop into an independent researcher in an intensive academic setting with a program of research focused on translational research to integrate biomarkers in bio-behavioral interventions to reduce and ameliorate symptoms in breast cancer survivors, particularly fatigue. Due to improvements in cancer treatments, survival rates have improved and, as such, there are an estimated 3.5 million breast cancer survivors as of 2016. Fatigue is one of the most commonly reported symptoms in cancer survivors. Radiation, a major contributor of fatigue, produces fatigue in 80% of survivors acutely and 33% of survivors long-term. Radiation is hypothesized to cause fatigue through pathways of inflammation; however, the mechanisms driving long-term fatigue (LTF) after treatment has ceased, is less clear. For breast cancer survivors, radiation can also cause reductions in heart function, which can produce LTF. Evidence also supports the role of oxidative stress in LTF. Given multiple pathways are likely involved in LTF in patients receiving radiation, biomarkers targeting different mechanisms may provide greater insight into the mechanisms leading to LTF and future interventions. Purpose: The purpose of this study is to explore biomarkers of oxidative stress (8-OH-dG), cardiac damage (cystatin-C), and inflammation (IL-6, CRP) in the development of LTF in cancer survivors diagnosed with breast cancer treated with radiation using the National Institutes of Health Symptom Science Model (NIH-SSM). Methods: We propose to leverage a matched, case-control design using serum samples from the Women’s Health Initiative (WHI) Life and Longevity After Cancer (LILAC). Women will be eligible if they meet the following criteria: 1) enrolled in LILAC, 2) have serum samples available at both WHI baseline and year 3, 3) breast cancer diagnosis and treatment between the two serum sample collection time points, and 4) fatigue measured at least 6 months from cancer treatment completion end date. Fatigue will be defined as scoring < 50 and “non-fatigued” defined as scoring ³ 50 measured using the Short-Form 36 Vitality subscale (SF-36). We anticipate having 150 fatigue cases and 150 non-fatigued controls. Serum biomarkers (cystatin-C, 8-OH-dG, IL-6, and CRP) will be measured using enzyme-linked immunosorbent assay (ELISA) at WHI baseline and year 3 of the WHI. Weighted sampling logistic regression models and mediation analyses will be used to test study aims.

项目摘要 这个Ruth L的目的。Kirschstein国家研究服务奖（NRSA）个人博士预科 护理研究奖学金（F31）的应用是为女士提供研究培训。 她在华盛顿大学读了一年的博士，并为博士后职位做准备。很长的- 本培训的长期目标是使申请人在密集的学术研究中发展成为独立的研究人员 设置一个研究计划，重点是转化研究，以整合生物行为学中的生物标志物。 干预措施，以减少和改善乳腺癌幸存者的症状，特别是疲劳。由于 癌症治疗的改善，生存率有所提高，因此，估计有3.5 截至2016年，乳腺癌幸存者达100万人。疲劳是癌症中最常见的症状之一 幸存者辐射是疲劳的主要因素，80%的幸存者急性疲劳，33%的幸存者急性疲劳。 长期生存。假设辐射通过炎症途径引起疲劳;然而， 治疗停止后驱动长期疲劳（LTF）的机制尚不清楚。乳腺癌 幸存者，辐射也会导致心脏功能下降，从而产生LTF。证据也支持 氧化应激在LTF中的作用。考虑到接受LTF治疗的患者中可能涉及多种途径， 辐射、针对不同机制的生物标志物可能会更深入地了解导致辐射的机制 长期信托基金和未来的干预措施。 目的：本研究旨在探讨氧化应激（8-OH-dG）、心肌损伤 在诊断为乳腺癌的癌症幸存者中，炎症（IL-6，CRP）和半胱氨酸蛋白酶抑制剂-C在LTF发展中的作用 使用美国国立卫生研究院症状科学模型（NIH-SSM）进行放射治疗的癌症。 方法：我们建议利用一个匹配的病例对照设计，使用来自妇女的血清样本， 健康倡议（WHI）癌症后的生命和长寿（LILAC）。符合以下条件的妇女将有资格参加 标准：1）入组LILAC，2）在WHI基线和第3年均具有血清样本，3）乳腺癌 在两个血清样本采集时间点之间的诊断和治疗，以及4）至少测量疲劳 自癌症治疗结束日期起6个月。疲劳将被定义为评分< 50和“非疲劳” 定义为使用简明健康量表36活力子量表（SF-36）测量的评分≥ 50。我们预计有150个 疲劳病例和150例非疲劳对照。将测定血清生物标志物（胱抑素-C、8-OH-dG、IL-6和CRP） 在WHI基线和WHI第3年使用酶联免疫吸附试验（ELISA）测量。加权 抽样逻辑回归模型和中介分析将用于测试研究目标。