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: 7145063
• 负责人: David Spiegel
• 金额: $ 48.79万
• 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/7145063
• 关键词: breast neoplasms; clinical research; cortisol; sleep

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，包括激素模式和睡眠，与乳腺癌发病率的风险增加和死亡率的更快进展有关。我们已经观察到，正常昼夜皮质醇节律的丧失与夜间更多的觉醒相关，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，在一个小鼠模型中，扰乱昼夜皮质醇周期会使植入的肿瘤生长加倍。最近也有证据表明，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流行的和乳腺癌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。我们还将研究睡眠模式与皮质醇，CRF，ACTH和褪黑激素的昼夜节律紊乱以及已知对乳腺癌进展显着的免疫功能的措施。这些是自然杀伤细胞的细胞毒性和特定的细胞因子：肿瘤坏死因子α和核因子κ 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和63名年龄和SES匹配的对照组，使用Actiwatch进行为期两周的家庭睡眠研究，并进行一晚的家庭EEG监测，随后进行32小时的监测。在综合临床研究中心进行睡眠监测和连续血液采样。这将提供与睡眠模式的全面评估相关的完整的昼夜节律激素评估。我们将这些措施与乳腺癌进展的后续过程。这项研究的结果将提供有关改善睡眠管理如何影响乳腺癌进程的具体证据。