Biobehavioral predictors of fatigue in newly-diagnosed breast cancer patients

新诊断乳腺癌患者疲劳的生物行为预测因子

• 批准号: 8246261
• 负责人: JULIENNE E BOWER
• 金额: $ 63.21万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-05 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8246261
• 关键词: Adjuvant Chemotherapy; Adverse effects; Aftercare; Behavior Therapy; Behavioral; Biologic Characteristic; Biological; Blood; Body mass index; Breast Cancer Treatment; Cancer Patient; Cancer Survivor; Cytokine Gene; Detection; Development; Diagnosis; Diagnostic; Distress; Early identification; Education; Ethnic group; Evaluation; Fatigue; Future; Gene Mutation; Genes; Genetic; Genetic Polymorphism; Glucocorticoids; Goals; Hydrocortisone; IL6 gene; Inflammation; Inflammatory; Interleukin-1; Intervention; Interview; Life; Life Stress; Long Term Survivorship; Longitudinal Studies; Malignant Neoplasms; Measures; Mediating; Mental Depression; Newly Diagnosed; Operative Surgical Procedures; Participant; Patient Self-Report; Patients; Prevalence; Process; Promoter Regions; Prospective Studies; Psychosocial Factor; Quality of life; Questionnaires; Radiation; Radiation therapy; Recording of previous events; Recruitment Activity; Reporting; Research; Research Design; Risk; Risk Factors; Saliva; Sampling; Signal Transduction; Single Nucleotide Polymorphism; Staging; Survival Rate; Symptoms; TNF gene; Trastuzumab; United States; Woman; base; biobehavior; cancer prevention; cancer therapy; chemotherapy; clinical practice; cytokine; experience; follow-up; hormone therapy; hypothalamic-pituitary-adrenal axis; inflammatory marker; malignant breast neoplasm; prevent; prospective; psychologic; psychosocial; therapy development; tumor

DESCRIPTION (provided by applicant): Fatigue is one of the most common and distressing side effects of breast cancer treatment and may persist for months or years after successful treatment completion. Approximately one-third of breast cancer survivors report moderate to severe symptoms of fatigue, which has a negative impact on all aspects of quality of life. Although the prevalence and impact of cancer-related fatigue has now been well established, very little is known about predictors and mechanisms for the development and persistence of fatigue post-treatment. Accordingly, the primary goal of this prospective, longitudinal study is to identify biological and psychological risk factors for post-treatment fatigue, with intensive evaluation of mechanisms, in women newly diagnosed with early stage breast cancer. In particular, this application focuses on vulnerability factors that increase risk for inflammatory processes given evidence suggesting an inflammatory basis for cancer-related fatigue. Specific aims are to: 1) determine whether inflammatory risk genes, hypothalamic-pituitary-adrenal axis dysregulation, and body mass index at treatment onset predict post-treatment fatigue in breast cancer patients assessed longitudinally for 18 months after treatment completion; 2) evaluate whether history of depression and early life stress at treatment onset predict post-treatment fatigue in breast cancer patients assessed longitudinally for 18 months after treatment onset; 3) investigate the contribution of measured proinflammatory cytokine activity to the association between biological and psychological risk factors and post-treatment fatigue. We will recruit 360 women with newly-diagnosed, early-stage breast cancer before initiation of treatment with radiation, chemotherapy, trastuzumab or endocrine therapy. At baseline, participants will complete self-report questionnaires, diagnostic interview for depression, blood draw for cytokine gene polymorphisms and markers of inflammation, and saliva samples for diurnal cortisol slope. Follow-up assessments conducted at treatment completion and at 6, 12, and 18 months post-treatment will determine the trajectory of post-treatment fatigue and associated changes in inflammatory processes. This research is a critical next step in the early identification of patients who are at risk for persistent fatigue as a long term side effect of cancer treatment and for the development and implementation of targeted interventions to prevent and treat this disabling symptom. PUBLIC HEALTH RELEVANCE: With advances in detection and treatment, the number of women who survive breast cancer has increased significantly in recent years. Many of these women will experience persistent, debilitating fatigue after completing cancer treatment. This research will identify risk factors for post-treatment fatigue and illuminate the biological underpinnings of this symptom, facilitating the early identification of vulnerable patients and the development and implementation of targeted therapies.

描述（由申请人提供）：疲劳是乳腺癌治疗最常见、最令人痛苦的副作用之一，在成功完成治疗后可能会持续数月或数年。大约三分之一的乳腺癌幸存者报告有中度至重度疲劳症状，这对生活质量的各个方面都有负面影响。尽管癌症相关疲劳的患病率和影响现已得到充分证实，但人们对治疗后疲劳发生和持续的预测因素和机制知之甚少。因此，这项前瞻性纵向研究的主要目标是在新诊断出早期乳腺癌的女性中确定治疗后疲劳的生物和心理危险因素，并对机制进行深入评估。特别是，鉴于有证据表明癌症相关疲劳的炎症基础，该应用重点关注增加炎症过程风险的脆弱因素。具体目标是：1）确定炎症风险基因、下丘脑-垂体-肾上腺轴失调和治疗开始时的体重指数是否可以预测乳腺癌患者在治疗完成后 18 个月的纵向评估的治疗后疲劳； 2）评估治疗开始后18个月纵向评估的乳腺癌患者的抑郁病史和治疗开始时的早期生活压力是否可以预测治疗后疲劳； 3) 研究测量的促炎细胞因子活性对生物和心理危险因素与治疗后疲劳之间关联的贡献。我们将招募 360 名新诊断的早期乳腺癌女性，然后开始接受放疗、化疗、曲妥珠单抗或内分泌治疗。在基线时，参与者将完成自我报告问卷、抑郁症诊断访谈、抽血检查细胞因子基因多态性和炎症标记物，以及唾液样本检查每日皮质醇斜率。治疗完成时以及治疗后 6、12 和 18 个月进行的随访评估将确定治疗后疲劳的轨迹以及炎症过程的相关变化。这项研究是早期识别因癌症治疗的长期副作用而面临持续疲劳风险的患者以及制定和实施有针对性的干预措施以预防和治疗这种致残症状的关键下一步。 公共卫生相关性：随着检测和治疗的进步，近年来乳腺癌存活的女性人数显着增加。其中许多女性在完成癌症治疗后会经历持续的、令人衰弱的疲劳。这项研究将确定治疗后疲劳的危险因素，并阐明这种症状的生物学基础，有助于早期识别易受影响的患者以及靶向治疗的开发和实施。