Biobehavioral predictors of fatigue in newly-diagnosed breast cancer patients

描述(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会持续数月或数年。大约三分之一的乳腺癌幸存者报告说有中度到重度的疲劳症状，这对生活质量的各个方面都有负面影响。虽然癌症相关性疲劳的流行和影响现在已经得到了很好的证实，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，这项前瞻性的纵向研究的主要目标是确定新诊断为早期乳腺癌的妇女治疗后疲劳的生物和心理危险因素，并对其机制进行深入评估。特别是，这项应用侧重于增加炎症过程风险的易损性因素，因为有证据表明癌症相关疲劳的炎症基础。具体目的是：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)评估治疗开始时的抑郁史和早期生活应激是否可以预测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在生物和心理危险因素与治疗后疲劳之间的关联中的作用。我们将招募360名新诊断的早期乳腺癌患者，然后开始接受放射、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，抑郁症的诊断性访谈，细胞因子基因多态性和炎症标志物的抽血，以及唾液样本的每日皮质醇斜率。在治疗完成时、治疗后6个月、12个月和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。这项研究是关键的下一步，以早期识别作为癌症治疗的长期副作用而存在持续性疲劳风险的患者，并开发和实施有针对性的干预措施来预防和治疗这种致残症状。

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.