Biobehavioral predictors of fatigue in newly-diagnosed breast cancer patients

描述（由申请人提供）：疲劳是乳腺癌治疗中最常见和最令人痛苦的副作用之一，在成功完成治疗后可能持续数月或数年。大约三分之一的乳腺癌幸存者报告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。虽然癌症相关疲劳的患病率和影响现已得到很好的确立，但对治疗后疲劳的发展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确定新诊断为早期乳腺癌的女性治疗后疲劳的生物学和心理学风险因素，并对机制进行深入评估。特别是，该应用程序侧重于增加炎症过程风险的脆弱性因素，因为有证据表明癌症相关疲劳的炎症基础。具体目标是：1）确定治疗开始时的炎症风险基因、下丘脑-垂体-肾上腺轴失调和体重指数是否预测治疗完成后18个月纵向评估的乳腺癌患者的治疗后疲劳; 2）评估治疗开始时的抑郁史和早期生活压力是否预测治疗开始后18个月纵向评估的乳腺癌患者的治疗后疲劳; 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的关联的贡献。我们将招募360名新诊断的早期乳腺癌女性患者，这些患者在开始放疗、化疗、曲妥珠单抗或内分泌治疗之前。在基线时，参与者将完成自我报告问卷，抑郁症诊断访谈，细胞因子基因多态性和炎症标志物的抽血，以及昼夜皮质醇斜率的唾液样本。在治疗完成时和治疗后6、12和18个月进行的随访评估将确定治疗后疲劳的轨迹和炎症过程的相关变化。这项研究是早期识别患有持续性疲劳风险的患者的关键下一步，这是癌症治疗的长期副作用，也是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步骤。 公共卫生相关性：随着检测和治疗的进步，近年来乳腺癌幸存妇女的人数大幅增加。这些女性中的许多人在完成癌症治疗后会经历持续的，使人衰弱的疲劳。这项研究将确定治疗后疲劳的风险因素，并阐明这种症状的生物学基础，促进脆弱患者的早期识别以及靶向治疗的开发和实施。

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.