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Grant Details

Grant Number: 5R01CA118567-05 Interpret this number
Primary Investigator: Spiegel, David
Organization: Stanford University
Project Title: Sleep, Circadian, Hormonal Dysregulation, and Breast Cancer Survival
Fiscal Year: 2010


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.


Evening salivary cortisol as a single stress marker in women with metastatic breast cancer.
Authors: Allende S. , Medina J.L. , Spiegel D. , Zeitzer J.M. .
Source: Psychoneuroendocrinology, 2020 05; 115, p. 104648.
EPub date: 2020-03-08.
PMID: 32171899
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Serotonin transporter polymorphism, depressive symptoms, and emotional impulsivity among advanced breast cancer patients.
Authors: Kim Y. , Carver C.S. , Hallmayer J.F. , Zeitzer J.M. , Palesh O. , Neri E. , Nouriani B. , Spiegel D. .
Source: Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, 2018 Apr; 26(4), p. 1181-1188.
EPub date: 2017-10-31.
PMID: 29090386
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Aberrant nocturnal cortisol and disease progression in women with breast cancer.
Authors: Zeitzer J.M. , Nouriani B. , Rissling M.B. , Sledge G.W. , Kaplan K.A. , Aasly L. , Palesh O. , Jo B. , Neri E. , Dhabhar F.S. , et al. .
Source: Breast cancer research and treatment, 2016 07; 158(1), p. 43-50.
EPub date: 2016-06-17.
PMID: 27314577
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Posttraumatic growth and diurnal cortisol slope among women with metastatic breast cancer.
Authors: Diaz M. , Aldridge-Gerry A. , Spiegel D. .
Source: Psychoneuroendocrinology, 2014 Jun; 44, p. 83-7.
EPub date: 2014-03-12.
PMID: 24767622
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Actigraphy-measured sleep disruption as a predictor of survival among women with advanced breast cancer.
Authors: Palesh O. , Aldridge-Gerry A. , Zeitzer J.M. , Koopman C. , Neri E. , Giese-Davis J. , Jo B. , Kraemer H. , Nouriani B. , Spiegel D. .
Source: Sleep, 2014-05-01; 37(5), p. 837-42.
EPub date: 2014-05-01.
PMID: 24790261
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Bedtime misalignment and progression of breast cancer.
Authors: Hahm B.J. , Jo B. , Dhabhar F.S. , Palesh O. , Aldridge-Gerry A. , Bajestan S.N. , Neri E. , Nouriani B. , Spiegel D. , Zeitzer J.M. .
Source: Chronobiology international, 2014 Mar; 31(2), p. 214-21.
EPub date: 2013-10-24.
PMID: 24156520
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Correspondence of plasma and salivary cortisol patterns in women with breast cancer.
Authors: Zeitzer J.M. , Nouriani B. , Neri E. , Spiegel D. .
Source: Neuroendocrinology, 2014; 100(2-3), p. 153-61.
EPub date: 2014-09-10.
PMID: 25228297
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Psychosocial correlates of sleep quality and architecture in women with metastatic breast cancer.
Authors: Aldridge-Gerry A. , Zeitzer J.M. , Palesh O.G. , Jo B. , Nouriani B. , Neri E. , Spiegel D. .
Source: Sleep medicine, 2013 Nov; 14(11), p. 1178-86.
EPub date: 2013-09-05.
PMID: 24074694
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Mind matters in cancer survival.
Authors: Spiegel D. .
Source: Psycho-oncology, 2012 Jun; 21(6), p. 588-93.
EPub date: 2012-03-21.
PMID: 22438289
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Mind matters in cancer survival.
Authors: Spiegel D. .
Source: JAMA, 2011-02-02; 305(5), p. 502-3.
PMID: 21285429
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Decrease in depression symptoms is associated with longer survival in patients with metastatic breast cancer: a secondary analysis.
Authors: Giese-Davis J. , Collie K. , Rancourt K.M. , Neri E. , Kraemer H.C. , Spiegel D. .
Source: Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2011-02-01; 29(4), p. 413-20.
EPub date: 2010-12-13.
PMID: 21149651
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Emotion modulation in PTSD: Clinical and neurobiological evidence for a dissociative subtype.
Authors: Lanius R.A. , Vermetten E. , Loewenstein R.J. , Brand B. , Schmahl C. , Bremner J.D. , Spiegel D. .
Source: The American journal of psychiatry, 2010 Jun; 167(6), p. 640-7.
EPub date: 2010-04-01.
PMID: 20360318
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Hypnotizability, posttraumatic stress, and depressive symptoms in metastatic breast cancer.
Authors: Keuroghlian A.S. , Butler L.D. , Neri E. , Spiegel D. .
Source: The International journal of clinical and experimental hypnosis, 2010 Jan; 58(1), p. 39-52.
PMID: 20183737
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Use and misuse of the consolidated standards of reporting trials (CONSORT) guidelines to assess research findings: comment on Coyne, Stefanek, and Palmer (2007).
Authors: Kraemer H.C. , Kuchler T. , Spiegel D. .
Source: Psychological bulletin, 2009 Mar; 135(2), p. 173-8; discussion 179-82.
PMID: 19254073
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Vagal regulation, cortisol, and sleep disruption in women with metastatic breast cancer.
Authors: Palesh O. , Zeitzer J.M. , Conrad A. , Giese-Davis J. , Mustian K.M. , Popek V. , Nga K. , Spiegel D. .
Source: Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, 2008-10-15; 4(5), p. 441-9.
PMID: 18853702
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Losing sleep over cancer.
Authors: Spiegel D. .
Source: Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2008-05-20; 26(15), p. 2431-2.
PMID: 18487562
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A longitudinal study of depression, pain, and stress as predictors of sleep disturbance among women with metastatic breast cancer.
Authors: Palesh O.G. , Collie K. , Batiuchok D. , Tilston J. , Koopman C. , Perlis M.L. , Butler L.D. , Carlson R. , Spiegel D. .
Source: Biological psychology, 2007 Apr; 75(1), p. 37-44.
EPub date: 2006-12-12.
PMID: 17166646
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Physical Activity and Survival in Women With Advanced Breast Cancer.
Authors: Palesh O. , Kamen C. , Sharp S. , Golden A. , Neri E. , Spiegel D. , Koopman C. .
Source: Cancer nursing, 2018 Jul/Aug; 41(4), p. E31-E38.
PMID: 28727578
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