Sleep, Circadian, Hormonal Dysregulation, and Breast Cancer Survival

睡眠、昼夜节律、荷尔蒙失调和乳腺癌生存

• 批准号: 7291027
• 负责人: David Spiegel
• 金额: $ 45.46万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-27 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7291027
• 关键词: Affect; Age; Anxiety; Blood specimen; Cancer Patient; Circadian Rhythms; Clinical Research; Corticotropin; Disruption; Electroencephalography; Emotional; Endocrine; Fatigue; Genes; Health; Home environment; Hormonal; Hormones; Hour; Hydrocortisone; Immune; Implant; Incidence; Laboratories; Malignant Neoplasms; Measures; Mediating; Melatonin; Mental Depression; Modeling; Monitor; Mus; NF-kappa B; Natural Killer Cells; Neurosecretory Systems; Outcome; Pain; Pattern; Phase; Polysomnography; Prognostic Factor; Recruitment Activity; Research; Risk; Sleep; Stress; Time; Tumor Necrosis Factor-alpha; Week; Woman; cytokine; cytotoxicity; immune function; improved; malignant breast neoplasm; mortality; response; shift work; social; stressor; tumor growth; tumor progression

DESCRIPTION (provided by applicant): Recent research provides evidence that disrupted circadian rhythms, including hormonal patterns and sleep, are associated with increased risk of breast cancer incidence and faster progression to mortality. We have observed that loss of normal diurnal cortisol rhythm associated with more awakenings during the night predicts early mortality with metastatic breast cancer. Other recent studies have shown that nighttime shift work is associated with higher breast cancer incidence, and in a murine model disrupting circadian cortisol cycles produced a doubling of implanted tumor growth. There is also recent evidence that abnormal clock genes are associated with cancer. However, it is not clear whether sleep disruption per se affects breast cancer progression, or whether such an effect is mediated by hormonal and immune dysregulation of this prevalent and hormone-mediated cancer. We propose to study sleep disruption as a prognostic factor in the progression of metastatic breast cancer. We will also examine sleep patterns in association with disrupted circadian rhythms of cortisol, CRF, ACTH, and melatonin as well as measures of immune function known to be salient to breast cancer progression. These are natural killer cell cytotoxicity and specific cytokines: tumor necrosis factor alpha and nuclear factor kappa B. We plan to recruit 117 women 55 and older with metastatic breast cancer and 63 age and SES-matched controls for a two-week at home sleep study using Actiwatch and one night of in-home EEG monitoring, followed by 32 hours of EEG sleep monitoring and continuous blood sampling in the General Clinical Research Center. This will provide full circadian hormone assessment associated with thorough assessment of sleep patterns. We will relate these measures to the subsequent course of breast cancer progression. Results of this study will provide specific evidence regarding how improved sleep management may affect the course of breast cancer.

描述（由申请人提供）：最近的研究提供的证据表明，昼夜节律紊乱（包括荷尔蒙模式和睡眠）与乳腺癌发病风险增加和死亡加速相关。我们观察到，正常昼夜皮质醇节律的丧失与夜间醒来次数增多可预测转移性乳腺癌的早期死亡率。最近的其他研究表明，夜班工作与较高的乳腺癌发病率有关，并且在小鼠模型中，破坏昼夜皮质醇周期会导致植入性肿瘤生长加倍。最近还有证据表明异常的时钟基因与癌症有关。然而，目前尚不清楚睡眠中断本身是否会影响乳腺癌的进展，或者这种影响是否是由这种普遍且由激素介导的癌症的激素和免疫失调介导的。我们建议研究睡眠中断作为转移性乳腺癌进展的预后因素。我们还将检查与皮质醇、CRF、ACTH 和褪黑激素的昼夜节律紊乱相关的睡眠模式，以及已知对乳腺癌进展至关重要的免疫功能测量。这些是自然杀伤细胞的细胞毒性和特定细胞因子：肿瘤坏死因子 α 和核因子 kappa B。我们计划招募 117 名 55 岁及以上患有转移性乳腺癌的女性以及 63 岁和 SES 匹配的对照者进行为期两周的家庭睡眠研究使用 Actiwatch 和一晚的家庭脑电图监测，然后在普通临床研究中心进行 32 小时的脑电图睡眠监测和连续血液采样。这将提供与睡眠模式彻底评估相关的完整昼夜节律激素评估。我们将把这些措施与乳腺癌的后续进展过程联系起来。这项研究的结果将提供关于改善睡眠管理如何影响乳腺癌病程的具体证据。