Sleep, Circadian Hormonal Dysregulation, and Breast Cancer Survival
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Study type: Observational

Summary: 
      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 a 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,
      ACTH, and melatonin as well as measures of immune function known to be salient to breast
      cancer progression. These are natural killer cell cytoxicity and specific cytokine, IL-6. We
      plan to recruit 105 women 45 years through 75 years with metastatic or recurrent breast
      cancer and 20 age and SES-matched controls for a two-week at home sleep study with Actiwatch
      and two nights of in-home EEG monitoring, followed by 28 hours of continuous blood sampling
      and one night of EEG sleep monitoring in our lab at Stanford. This will provide a full
      examination of circadian hormones associated with sleep patterns. We will relate these
      assessments 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. Aim 1: To study 24-hr diurnal rhythms of HPA axis hormones and melatonin in
      women with metastatic or recurrent breast cancer. Hypothesis 1: Women with metastatic or
      recurrent breast cancer will have reduced amplitude and disrupted phase of 24-hr diurnal
      rhythms of cortisol, ACTH, and melatonin. Aim 2: To describe sleep disruption in women with
      metastatic breast cancer and examine psychosocial, endocrine, and immune factors that may be
      associated with sleep disruption. Hypothesis 2: Women with metastatic or recurrent breast
      cancer will have a higher incidence of both at home and laboratory-examined sleep disruption
      than control women without breast cancer. Hypothesis 3: Poorer sleep quality will be
      associated with more pain, more emotional suppression in response to stressors, less
      emotional support, greater depression and anxiety, and greater perceived and traumatic
      stress. Hypothesis 4: Poorer sleep quality and quantity of sleep and daytime sleepiness and
      fatigue will be associated with abnormal circadian neuroendocrine (i.e., cortisol, ACTH, and
      melatonin) and immune patterns (i.e., suppressed day and night time NK activity and loss of
      NK rhythms; increased day time IL-6 levels and /or loss of IL-6 rhythm). Aim 3: To study the
      relationship between sleep disruption and survival time among metastatic and recurrent breast
      cancer patients. Hypothesis 5: Poorer sleep quality and quantity of sleep will predict
      shorter survival. Hypothesis 6: Reduced diurnal amplitude and an abnormal phase of cortisol
      will predict shorter survival. Explanatory Aim 4: To investigate whether sleep disruption
      mediates the relation of psychosocial factors to health outcomes.
    


Intervention name(s): Urine sample; Electrode sleep recorder; phlebotomy
Intervention type(s): Procedure; Device; Procedure
Intervention description(s): Standard of care; Standard of care; Standard of care
Other intervention name(s): urine test; Digital sleep recorder; blood draw
Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        women with breast cancer
      
Biospecimen description: 
      Saliva and blood