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. ? ? ?
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