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Accelerated biological aging in breast cancer and risk for cognitive and physical complaints

乳腺癌的生物衰老加速以及认知和身体不适的风险

基本信息

批准号：
9888179
负责人：
JULIENNE E BOWER
金额：
$ 64.74万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-01-01 至 2023-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9888179
关键词：
Acute Address Adjuvant Therapy Aftercare Age Aging Behavior assessment Biological Biological Aging Biological Markers Biological Process Biology of Aging Blood Blood specimen Brain Breast Cancer Patient Breast Cancer Risk Factor Breast Cancer Treatment Breast Cancer survivor Cancer Detection Cancer Patient Cancer Survivor Cell Aging Cells Chemotherapy and/or radiation Chronic Clinical Cognition Cognitive Collection DNA DNA Damage DNA analysis Data Data Reporting Detection Development Epigenetic Process Exhibits Exposure to Fatigue Funding Future Health Impaired cognition Impairment Individual Inflammation Inflammatory Intervention Lead Long-Term Effects Longitudinal Studies Malignant Neoplasms Measures Mediating Mediator of activation protein Messenger RNA Morbidity - disease rate Operative Surgical Procedures Outcome Pain Parents Participant Pathway interactions Patient Self-Report Patients Persistent pain Personal Satisfaction Phenotype Physical Function Physical activity Plasma Population Prevention Process Prospective Studies Public Health Quality of life RNA RNA analysis Radiation Radiation therapy Recovery Reporting Research Risk Role SF-36 Signal Transduction Source Specimen Survivors Symptoms Testing Toxic effect Translational Research United States Visit Woman Work age related cancer therapy chemotherapy cognitive function cohort common treatment cytotoxic design early onset experience follow-up genomic biomarker hormone therapy improved indexing inflammatory marker innovation malignant breast neoplasm physical conditioning prospective rate of change reduce symptoms senescence survivorship therapy design

项目摘要

Project summary Breast cancer is the most common cancer in women, with over two-hundred and sixty thousand new cases expected in the United States in 2018 alone. There are estimated to be more than 3 million breast cancer survivors in the US due to substantial advances in detection and treatment, with this number continuing to grow. However, treatments also increase risk for long-term and late toxicities, including effects on physical and cognitive function that interfere with quality of life. One possible explanation recently proposed is that the toxicity of cancer treatments may directly accelerate the aging process in some patients, leading to earlier onset of age-related symptoms such as cognitive complaints, fatigue, declines in physical function, and lasting pain. However, this hypothesis has not been rigorously tested in clinical populations. Our study will examine the effects of common breast cancer treatments as they relate to markers of biological aging, inflammation, and reports of physical and cognitive complaints in a prospective study of breast cancer patients assessed prior to and after exposure to chemotherapy and/or radiotherapy. The proposed study will leverage an existing NCI- funded cohort of women with early-stage breast cancer assessed before onset of adjuvant therapy with radiation (RT), chemotherapy (CT), or endocrine therapy and again after completion of RT and/or CT and at follow-up visits occurring 6-, 12-, and 18-month post-treatment, with serial blood specimens for plasma, DNA and RNA analyses. In this well characterized cohort of breast cancer survivors, we propose to add the assessment of markers of biological aging using existing collected specimens and add a new behavioral assessment at 7 years post treatment to 1) examine the effects of breast cancer treatments on the biological aging process, 2) test the relationship between accelerated biological aging and cognitive and physical complaints in breast cancer patients over the follow-up period, and 3) test whether inflammatory factors mediate the relationship between biological aging and cognitive and physical complaints.

项目概要乳腺癌是女性最常见的癌症，新增病例超过两十六万例仅 2018 年就预计在美国实现这一目标。估计有超过300万乳腺癌患者由于检测和治疗方面的巨大进步，美国的幸存者数量仍在继续增加生长。然而，治疗也会增加长期和晚期毒性的风险，包括对身体和身体的影响。干扰生活质量的认知功能。最近提出的一种可能的解释是癌症治疗的毒性可能会直接加速一些患者的衰老过程，导致发病更早与年龄相关的症状，如认知障碍、疲劳、身体机能下降和持续疼痛。然而，这一假设尚未在临床人群中得到严格测试。我们的研究将考察常见乳腺癌治疗的效果，因为它们与生物衰老、炎症和癌症标志物有关在一项针对乳腺癌患者的前瞻性研究中评估的身体和认知问题的报告以及接受化疗和/或放疗后。拟议的研究将利用现有的 NCI- 资助的早期乳腺癌女性队列在辅助治疗开始前进行评估放疗 (RT)、化疗 (CT) 或内分泌治疗，以及在完成 RT 和/或 CT 后再次进行治疗后 6、12 和 18 个月进行随访，收集血浆、DNA 的连续血液样本和RNA分析。在这个特征明确的乳腺癌幸存者队列中，我们建议添加使用现有收集的样本评估生物衰老标记并添加新的行为治疗后 7 年进行评估，以 1) 检查乳腺癌治疗对生物学的影响衰老过程，2）测试加速生物衰老与认知和身体的关系乳腺癌患者在随访期间的主诉，以及 3) 测试炎症因子是否调节生物衰老与认知和身体不适之间的关系。