Official Title: “Sleep, Circadian, Hormonal Dysregulation, and Breast Cancer Survival”

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 rhythym 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 cleat whether sleep disruption per se affects creast 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 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 the Stanford University General Clinical Research Center. 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 HRA 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 rhythyms of cortisol, CRF, 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 neuroenddocrine (i.e., cortisol, CRF, ACTH, and melatonin) and immune patterns (i.e., suppressed day and night time NK activity and loss of NK rhythyms; increased day time IL-6 levels and /or loss of IL-6 rhythym).

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 dinural 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.

Study Type: Observational

Study Design: Other

Intervention(s) in this Clinical Trial

• Procedure: Urine sample
• Behavioral: Questionnaire
• Device: Electrode sleep recorder
• Device: Activity watch
• Procedure: phlebotomy

Inclusion Criteria:Inclusion criteria for breast cancer participants:

• 1. Female
• 2. Between 45 and 54 years old
• 3. Documented metastatic or recurrent breast cancer
• 4. Karnofsky rating of at least 70% (measure of physical ability used to assess medically ill patients)
• 5. Residence within the Greater San Francisco Bay Area
• 6. Proficiency in English sufficient to complete questionnaires
• 7. Patients# willingness to go through a 30 day washout period if they are currently on decadron (depending on the dose, may be able to reduce 30 days to 2 weeks)
• 8. Postmenopausal
• 9. Non smokers (occasional smoking will be ok, they need to agree to stop smoking during study participation. If smoking cessation will cause withdrawal, they can not participate).
• 10. Positive supraclavicular lymph nodes as the only metastatic lesion at the time of initial diagnosis.
• 11. No history of Deep Vein Thrombosis.
• 12. If taking Benzodiazepines, patients' willingness tostop2 days before the collection of physiological measures, such as the 2 week at home sleep recordings and then the 2 days at the GCRC.
• 13. Agree to catheterization for blood sample collection.
• 14. Has graduated high school or obtained GED.

Eligibility-inclusion for healthy controls:

• 1. Female
• 2. 55 or older
• 3. No history of breast cancer
• 4. Residence within the Greater San Francisco Bay Area
• 5. Proficiency in English to complete questionnaires
• 6. Post Menopausal
• 7. Non-smokers (occasional smoking will be ok, they need to agree to stop smoking during study participation. If smoking cessation will cause withdrawal, they can not participate).
• 8. No history of Deep Vein Thrombosis.


Exclusion Criteria:Exclusion criteria for breast cancer participants:

• 1. Other active cancers within the past 10 years other than breast cancer, basal cell or squamous cell carcinomas of the skin, or in situ cancer of the cervix
• 2. Concurrent medical condition likely to influence short term survival
• 3. Utilization of a corticosteroid, including glucocorticoids as a treatment for side effects of chemotherapy, within the 2 preceding weeks.
• 4. History of major psychiatric illness that required hospitalization or medication
• 5. Substance Dependence or abuse
• 6. Travel involving two or more time zones or shift work (working a non-traditional schedule: e.g., 4pm#midnight or 10pm#6am) in the last two weeks prior to the entry of the study
• 7. Low hematocrit (up to the discression of the PI, may be able to participate in parts of the protocol)
• 8. Bilateral lymph nodes removed.
• 9. Diagnosis of diabetis (need to check with PI, some mild cases of diabetes may be ok).

Exclusion criteria for healthy controls:

• 1. Concurrent medical condition likely to influence short term survival
• 2. Utilization of a corticosteroid within the 2 preceding weeks
• 3. History of major psychiatric illness that required hospitalization or medication
• 4. Substance dependence or abuse
• 5. Travel involving two or more time zones or shift work (working a non-traditional schedule: e.g., 4pm#midnight or 10pm#6am) in the last two weeks prior to the entry of the study
• 6. First degree relative with breast cancer history
• 7. Low hematocrit (up to the discression of the PI, may be able to participate in parts of the protocol).

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 45 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: Stanford University

Overall Clinical Trial Officials and Contacts

David Spiegel Principal Investigator Stanford University  

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00519168

Study ID Number: BRSADJ0013

ClinicalTrials.gov Identifier: NCT00519168

Health Authority: United States: Food and Drug Administration