SLEEP, CIRCADIAN HORMONAL DYSREGULATION AND BREAST CANCER SURVIVAL

睡眠、昼夜荷尔蒙失调与乳腺癌生存

• 批准号: 7717933
• 负责人: David Spiegel
• 金额: $ 0.17万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-12-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7717933
• 关键词: Address; Affective; Age; Aging; Anxiety; Anxiety Disorders; Breast Cancer Risk Factor; Cancer Etiology; Cancer Patient; Cessation of life; Circadian Rhythms; Computer Retrieval of Information on Scientific Projects Database; Corticotropin; Corticotropin-Releasing Hormone; Development; Disease; Disease Progression; Disruption; Elderly; Endocrine; Fatigue; Feeling; Functional disorder; Funding; Gene Expression; Grant; HPSE gene; Health; Homeostasis; Hormonal; Hormones; Human; Hydrocortisone; Immune; Immunologic Markers; Implant; Incidence; Institution; Lead; Life; Link; Long-Term Survivors; Longevity; Malignant Neoplasms; Measures; Mediating; Mediator of activation protein; Melatonin; Mental Depression; Metastatic Neoplasm to the Breast; Modeling; Mus; Natural Killer Cells; Obstructive Sleep Apnea; Outcome; Pain; Patient Self-Report; Patients; Pattern; Physiological; Play; Postmenopause; Process; Prognostic Factor; Psychosocial Factor; Quality of life; Recovery; Research; Research Personnel; Resistance; Resources; Restless Legs Syndrome; Risk; Role; Sleep; Sleep Disorders; Sleeplessness; Social support; Source; Spouses; Stimulus; Stress; Structure; Substance abuse problem; Symptoms; System; Time; United States National Institutes of Health; Woman; body-mind; circadian pacemaker; coping; day; depressive symptoms; experience; hypothalamic-pituitary-adrenal axis; immune function; improved; malignant breast neoplasm; mortality; outcome forecast; psychosocial; relating to nervous system; shift work; tumor growth

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We spend one-third of our lives asleep, yet little research has been done on the effects of sleep on resistance to cancer incidence and progression. There is a high incidence (63%) of self-reported sleep disruption in women with breast cancer and this has been shown to be associated with decreased longevity in these patients. While this association could be driven by more severe cancer causing an increase in sleep disruption, it is also possible that sleep disruption could lead to decreased survival time in these patients. It has been shown that women whose sleep is disrupted by nighttime shiftwork are at higher risk for breast cancer. Other types of sleep disruption common in post-menopausal women, such as obstructive sleep apnea, restless legs syndrome, and insomnia, could also have significant deleterious effects on longevity. Sleep is a critical time for energy conservation and neural homeostasis. The disruption of these processes could, very likely, lead to dysfunction of the nervous, endocrine, immune and other systems. Furthermore, disrupted sleep is often treatable, providing a potentially powerful means of improving both the quality of life and the prognosis of cancer patients. A growing body of evidence suggests that psychosocial factors have potentially powerful modulating effects on the course of cancer. Sleep may play a central role. There is growing scientific evidence and increasing public concern regarding the link between stress and health. One of the major consequences of stress is disruption of circadian rhythms, including the timing and structure of sleep and hormonal activity. Recent research indicates that such disruption predicts poor prognosis for breast cancer patients, and thus may be a mediating mind-body mechanism linking stress to disease progression. Disrupted sleep is important for its immediate consequences, such as fatigue, development of depressive and anxiety disorders, increased substance abuse, and reduced social support from spouses/partners as well as for its long-term consequences. Sleep is essential to human functioning and to disease recovery. Sleep problems are persistent among long-term survivors of breast cancer, and are associated with a poorer quality of life. Undisturbed sleep appears essential for coping with cancer and symptoms such as pain, because disturbed sleep causes decrements in the functioning of physiological systems critical to cancer defense, such as natural killer cell activity and lowers the threshold for experiencing negative stimuli and feelings. However, little is known about specific affective or psychosocial factors that may precede or influence disrupted sleep for women with breast cancer. There were 211,300 new cases of breast cancer in the US in 2003 and 39,800 deaths due to the disease. Breast cancer is largely a disease of aging, rare below the age of 50, and increasingly common with advancing age. Recent research provides evidence that disrupted circadian rhythms are associated with increased risk of breast cancer incidence and faster progression to mortality. We have observed that loss of normal diurnal cortisol rhythm, with peaks late in the day rather than, as normal, in the morning, predicts early mortality with breast cancer. This disrupted rhythm is associated with more awakenings during the night, with the increased awakenings, perhaps, even contributing to the sustained disruption of the cortisol rhythm. Recent studies have shown that nighttime shift work is associated with a higher risk of developing breast cancer. In a murine model, disrupting circadian cycles, including cortisol, produced a doubling of implanted tumor growth. There is evidence that abnormal circadian clock gene expression is associated with cancer. Thus, sleep disruption is a potentially modifiable mediating risk factor for breast cancer and its progression. We therefore propose to study sleep disruption as a prognostic factor in the progression of metastatic breast cancer, and its association with disrupted circadian patterns of cortisol, corticotropin releasing factor (CRF), ACTH, melatonin, and measures of immune function. The project has four Specific Aims with 6 Hypotheses. To address Aim 1, we will compare sleep and diurnal hormone patterns in 105 women with metastatic breast cancer to 25 age- and SES-matched healthy controls. For Aim 2, we will study the association between the sleep patterns of these 105 women with metastatic breast cancer and various psychosocial and physiological factors. For Aim 3, we will examine the sleep patterns of these 105 women with metastatic breast cancer and follow them throughout the progression of their disease to determine whether disrupted sleep predicts shorter survival. For Aim 4, we will conduct exploratory mediator analyses to investigate whether sleep disruption mediates the relation of psychosocial factors (such as depression, anxiety) to health outcomes (HPA axis measures, immune markers and ultimately survival).

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