Proinflammatory Biomarkers and Post-Breast CancerLymphedema

促炎生物标志物和乳腺癌后淋巴水肿

• 批准号: 8047759
• 负责人: Mei Rosemary Fu
• 金额: $ 33.02万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-15 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8047759
• 关键词: Adverse effects; Affect; Animal Model; Area; Biological Markers; Body Composition; Body mass index; Breast; Breast Cancer Treatment; Burn injury; Cancer Survivor; Candidate Disease Gene; Data; Detection; Development; Diagnosis; Distress; Evaluation; Excision; Future; Gene Expression; Genetic; Genetic Polymorphism; Genetic Variation; Genotype; Growth Factor; Health Personnel; IL6 gene; IL8 gene; Incidence; Individual; Infection; Inflammation; Inflammatory; Injury; Interleukin-1; Interleukin-10; Intervention; Knowledge; Life; Limb structure; Liquid substance; Lymph; Lymphangiogenesis; Lymphatic; Lymphatic System; Lymphedema; Malignant Neoplasms; Measures; Minor; Morbidity - disease rate; Newly Diagnosed; Obesity; Operative Surgical Procedures; Pain; Patient Self-Report; Patients; Pattern; Predisposition; Prevention; Process; Proteins; Publishing; Quality of life; Radiosurgery; Recruitment Activity; Reporting; Research; Risk; Role; Sampling; Survivors; Swelling; Symptoms; Syndrome; Testing; Tissues; Trauma; Tumor Necrosis Factor-alpha; United States; Vascular Endothelial Growth Factor C; Vascular Endothelial Growth Factor D; Woman; base; cancer therapy; cytokine; design; experience; high risk; insight; interstitial; lifetime risk; lymph nodes; malignant breast neoplasm; prevent; prospective; psychologic; response; social

DESCRIPTION (provided by applicant): Among the 2.5 million breast cancer survivors in the U.S. more than 40% of them have developed lymphedema (LE). Post-breast cancer LE, a syndrome of abnormal swelling and multiple distressing symptoms, is caused by injuries to the lymphatic system from cancer treatment. As advances in cancer treatment lengthen survival, LE has emerged as a high-impact long-term morbidity that profoundly impairs survivors' quality of life. All women undergoing breast cancer treatment are at lifetime risk for LE. While removal of lymph nodes, surgery, and radiation are the major causal factors for LE, cancer treatment is necessary for life-saving. Recent research has revealed that inflammation-infection and higher body mass index (BMI) are the main predictors of LE besides treatment-related risk. Unfortunately, these studies did not evaluate biomarkers known for inflammation, and thus the role of inflammation-infection in limb volume change (LVC) and LE development could not be ascertained. Elevated levels of proinflammatory biomarkers have been speculated to be associated with inflammation in patients with LE. Moreover, genetic variations may be one of the important factors that influence breast cancer survivors' responses to inflammatory processes and vulnerability to LE, including survivors' responses to treatment-related trauma (such as surgery and radiation) and triggering factors (such as infection, burns, minor injuries, and higher BMI or obesity). The purpose of this exploratory project is to prospectively examine levels and patterns of proinflammatory biomarkers and genetic variations in relation to LVC measured with the infra-red perometer-400T/350S over a 12-month period in breast cancer survivors who are at risk for LE. The project will employ a prospective, descriptive, and repeated-measure design. A sample of 120 women who are newly diagnosed and treated for invasive breast cancer will be recruited. Data will be collected over a 12-month period, including: (1) measuring and comparing LVC using the infra-red perometer, LE symptoms, BMI and body composition; (2) evaluating levels and patterns of proinflammatory biomarkers in relation to LVC; and (3) evaluating genotypes known for inflammation in relation to LVC. These proinflammatory biomarkers and candidate genes include lymphatic specific growth factors (VEGF-C & VEGF-D), cytokines (IL1-a, IL1-b, IL6, IL8, & IL10), and tumor necrosis factor-a. This project is an important first step toward gaining necessary knowledge and insights into breast cancer survivors' susceptibility, which may help to identify survivors at higher risk based on individual survivors' biomarker patterns and genetic factors. Findings of the project are fundamental in developing and testing more intense and personalized interventions to prevent and treat LE among the breast cancer survivors. PUBLIC HEALTH RELEVANCE: Lymphedema, a syndrome of abnormal swelling and multiple distressing symptoms, is a major adverse effect of breast cancer treatment, which can cause long-term physical, psychological, social, and financial problems. The purpose of this exploratory project is to prospectively examine levels and patterns of proinflammatory biomarkers and genetic variations in relation to limb volume changes measured with the infra-red perometer- 400T/350S over a 12-month period in breast cancer survivors. This project is an important first step toward gaining necessary knowledge and insights into breast cancer survivors' susceptibility, which may help to identify survivors at higher risk based on individual survivors' biomarker patterns and genetic factors and potentially target the survivors at higher risk for more intense and personalized interventions to prevent and treat lymphedema.

描述（由申请人提供）：在美国的250万乳腺癌幸存者中，有40％以上的淋巴水肿（LE）。胸癌后癌症是一种异常肿胀和多种困扰症状的综合征，是由癌症治疗对淋巴系统受伤引起的。随着癌症治疗的进展延长了生存，LE已成为一种高影响的长期发病率，严重损害了幸存者的生活质量。所有接受乳腺癌治疗的妇女都有LE的终生风险。 虽然去除淋巴结，手术和辐射是LE的主要因素，但癌症治疗对于挽救生命是必要的。最近的研究表明，除了与治疗相关的风险外，炎症感染和更高的体重指数（BMI）是LE的主要预测指标。不幸的是，这些研究没有评估以炎症而闻名的生物标志物，因此无法确定炎症感染在肢体体积变化（LVC）中的作用和发育。据推测，促炎生物标志物的水平升高与LE患者的炎症有关。此外，遗传变异可能是影响乳腺癌幸存者对炎症过程的反应和对LE的脆弱性的重要因素之一，包括幸存者对治疗相关的创伤（例如手术和放射线）的反应以及触发因素（例如感染，烧伤，次要，轻伤，以及更高的BMI或BMI或更高的BMI）。 该探索性项目的目的是前瞻性地检查促炎生物标志物的水平和模式，以及与乳腺癌幸存者在12个月内用Infra-Red Permeter-400T/350在有LE风险的乳腺癌幸存者中测得的LVC的遗传变异。该项目将采用潜在的，描述性和重复量的设计。将招募120名新诊断和治疗的女性，这些样本将被招募。数据将在12个月的时间内收集，包括：（1）使用Infra-Red Perometer，LE症状，BMI和身体组成测量和比较LVC； （2）评估与LVC相关的促炎生物标志物的水平和模式； （3）评估与LVC相关的炎症已知的基因型。这些促炎的生物标志物和候选基因包括淋巴特异性生长因子（VEGF-C＆VEGF-D），细胞因子（IL1-A，IL1-B，IL6，IL6，IL8和IL10）和肿瘤坏死因子-A。 该项目是获得必要的知识和洞察乳腺癌幸存者敏感性的重要第一步，这可能有助于根据个别幸存者的生物标志物模式和遗传因素确定较高风险的幸存者。该项目的发现是开发和测试更激烈和个性化的干预措施，以预防和治疗乳腺癌幸存者中的LE。 公共卫生相关性：淋巴水肿，一种异常肿胀和多种痛苦症状的综合征，是乳腺癌治疗的主要不良影响，可能导致长期的身体，心理，社会和财务问题。该探索性项目的目的是前瞻性地检查促炎生物标志物的水平和模式，以及与乳腺癌幸存者12个月内通过Infra-Red Permoter-400T/350s测得的肢体体积变化有关的遗传变化。该项目是获得必要的知识和洞察乳腺癌幸存者敏感性的重要第一步，这可能有助于确定基于个别幸存者的生物标志物模式和遗传因素的较高风险的幸存者，并有可能针对更高的风险，以较高的风险，以预防和治疗淋巴水肿。