Breast Cancer Research and Treatment

, Volume 162, Issue 3, pp 581–589 | Cite as

Sleep duration and breast cancer prognosis: perspectives from the Women’s Healthy Eating and Living Study

  • Catherine R. Marinac
  • Sandahl H. Nelson
  • Shirley W. Flatt
  • Loki Natarajan
  • John P. Pierce
  • Ruth E. Patterson



To examine whether baseline sleep duration or changes in sleep duration are associated with breast cancer prognosis among early-stage breast cancer survivors in the multi-center Women’s Healthy Eating and Living Study.


Data were collected from 1995 to 2010. Analysis included 3047 women. Sleep duration was self-reported at baseline and follow-up intervals. Cox proportional hazard models were used to investigate whether baseline sleep duration was associated with breast cancer recurrence, breast cancer-specific mortality, and all-cause mortality. Time-varying models investigated whether changes in sleep duration were associated with breast cancer prognosis.


Compared to women who slept 7–8 h/night at baseline, sleeping ≥9 h/night was associated with a 48% increased risk of breast cancer recurrence (Hazard ratio [HR] 1.48, 95% Confidence interval [CI] 1.01, 2.00), a 52% increased risk of breast cancer-specific mortality (HR 1.52, 95% CI 1.09, 2.13), and a 43% greater risk of all-cause mortality (HR 1.43, 95% CI 1.07, 1.92). Time-varying models showed analogous increased risk in those who inconsistently slept ≥9 h/night (all P < 0.05), but not in those who consistently slept ≥9 h/night.


Consistent long or short sleep, which may reflect inter-individual variability in the need for sleep, does not appear to influence prognosis among early-stage breast cancer survivors.


Sleep Longitudinal modeling Survival Survivorship 



Dr. Marinac was supported by the National Cancer Institute of the National Institutes of Health under award number F31 CA183125. Research support was also provided by funding from the National Cancer Institute under award numbers U54 CA155435, and R01 CA166293. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Compliance with ethical standards

Conflict of interest

The authors have no financial or conflicts of interest to disclose.

Ethical Approval

All procedures performed involving human participants were in accordance with the ethical standards of the University of California, San Diego and 6 other clinical sites, and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.


  1. 1.
    Howlander N, Noone A, Krapacho M, Miller D, Boship K, Alterkruse SF, C.L. K, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, E.J. F, Cronin KA SEER Cancer Statistics Revier, 1975–2013, National Cancer Institute. Bethesda, MD. Based on November 2015 SEER data submission, posted to the SEER web site, April 2016
  2. 2.
    Bower JE (2008) Behavioral symptoms in patients with breast cancer and survivors. J Clin Oncol 26(5):768–777. doi: 10.1200/JCO.2007.14.3248 PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Alfano CM, Lichstein KL, Vander Wal GS, Smith AW, Reeve BB, McTiernan A, Bernstein L, Baumgartner KB, Ballard-Barbash R (2011) Sleep duration change across breast cancer survivorship: associations with symptoms and health-related quality of life. Breast Cancer Res Treat 130(1):243–254. doi: 10.1007/s10549-011-1530-2 PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Tamakoshi A, Ohno Y, Group JS (2004) Self-reported sleep duration as a predictor of all-cause mortality: results from the JACC study, Japan. Sleep 27(1):51–54PubMedGoogle Scholar
  5. 5.
    Patel SR, Ayas NT, Malhotra MR, White DP, Schernhammer ES, Speizer FE, Stampfer MJ, Hu FB (2004) A prospective study of sleep duration and mortality risk in women. Sleep 27(3):440–444PubMedGoogle Scholar
  6. 6.
    Hublin C, Partinen M, Koskenvuo M, Kaprio J (2007) Sleep and mortality: a population-based 22-year follow-up study. Sleep 30(10):1245–1253PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Spiegel K, Leproult R, Van Cauter E (1999) Impact of sleep debt on metabolic and endocrine function. Lancet 354(9188):1435–1439. doi: 10.1016/S0140-6736(99)01376-8 PubMedCrossRefGoogle Scholar
  8. 8.
    Vgontzas AN, Zoumakis E, Bixler EO, Lin HM, Follett H, Kales A, Chrousos GP (2004) Adverse effects of modest sleep restriction on sleepiness, performance, and inflammatory cytokines. J Clin Endocrinol Metab 89(5):2119–2126. doi: 10.1210/jc.2003-031562 PubMedCrossRefGoogle Scholar
  9. 9.
    Meier-Ewert HK, Ridker PM, Rifai N, Regan MM, Price NJ, Dinges DF, Mullington JM (2004) Effect of sleep loss on C-reactive protein, an inflammatory marker of cardiovascular risk. J Am Coll Cardiol 43(4):678–683. doi: 10.1016/j.jacc.2003.07.050 PubMedCrossRefGoogle Scholar
  10. 10.
    Morris CJ, Aeschbach D, Scheer FA (2012) Circadian system, sleep and endocrinology. Mol Cell Endocrinol 349(1):91–104. doi: 10.1016/j.mce.2011.09.003 PubMedCrossRefGoogle Scholar
  11. 11.
    Schernhammer ES, Kroenke CH, Laden F, Hankinson SE (2006) Night work and risk of breast cancer. Epidemiology 17(1):108–111PubMedCrossRefGoogle Scholar
  12. 12.
    Megdal SP, Kroenke CH, Laden F, Pukkala E, Schernhammer ES (2005) Night work and breast cancer risk: a systematic review and meta-analysis. Eur J Cancer 41(13):2023–2032. doi: 10.1016/j.ejca.2005.05.010 PubMedCrossRefGoogle Scholar
  13. 13.
    Vijayalaxmi Thomas CR Jr, Reiter RJ, Herman TS (2002) Melatonin: from basic research to cancer treatment clinics. J Clin Oncol 20(10):2575–2601. doi: 10.1200/JCO.2002.11.004 PubMedCrossRefGoogle Scholar
  14. 14.
    Dimitrov S, Lange T, Nohroudi K, Born J (2007) Number and function of circulating human antigen presenting cells regulated by sleep. Sleep 30(4):401–411PubMedCrossRefGoogle Scholar
  15. 15.
    Phipps AI, Bhatti P, Neuhouser ML, Chen C, Crane TE, Kroenke CH, Ochs-Balcom H, Rissling M, Snively BM, Stefanick ML, Treggiari MM, Watson NF (2016) Pre-diagnostic sleep duration and sleep quality in relation to subsequent cancer survival. J Clin Sleep Med 12(4):495–503. doi: 10.5664/jcsm.5674 PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Costa AR, Fontes F, Pereira S, Goncalves M, Azevedo A, Lunet N (2014) Impact of breast cancer treatments on sleep disturbances—a systematic review. Breast 23(6):697–709. doi: 10.1016/j.breast.2014.09.003 PubMedCrossRefGoogle Scholar
  17. 17.
    Savard J, Davidson JR, Ivers H, Quesnel C, Rioux D, Dupere V, Lasnier M, Simard S, Morin CM (2004) The association between nocturnal hot flashes and sleep in breast cancer survivors. J Pain Symptom Manag 27(6):513–522. doi: 10.1016/j.jpainsymman.2003.10.013 CrossRefGoogle Scholar
  18. 18.
    Palesh O, Aldridge-Gerry A, Zeitzer JM, Koopman C, Neri E, Giese-Davis J, Jo B, Kraemer H, Nouriani B, Spiegel D (2014) Actigraphy-measured sleep disruption as a predictor of survival among women with advanced breast cancer. Sleep 37(5):837–842. doi: 10.5665/sleep.3642 PubMedPubMedCentralGoogle Scholar
  19. 19.
    Hahm BJ, Jo B, Dhabhar FS, Palesh O, Aldridge-Gerry A, Bajestan SN, Neri E, Nouriani B, Spiegel D, Zeitzer JM (2014) Bedtime misalignment and progression of breast cancer. Chronobiol Int 31(2):214–221. doi: 10.3109/07420528.2013.842575 PubMedCrossRefGoogle Scholar
  20. 20.
    Pierce JP, Faerber S, Wright FA, Rock CL, Newman V, Flatt SW, Kealey S, Jones VE, Caan BJ, Gold EB, Haan M, Hollenbach KA, Jones L, Marshall JR, Ritenbaugh C, Stefanick ML, Thomson C, Wasserman L, Natarajan L, Thomas RG, Gilpin EA, Women’s Healthy E, Living study g (2002) A randomized trial of the effect of a plant-based dietary pattern on additional breast cancer events and survival: the Women’s Healthy Eating and Living (WHEL) Study. Control Clin Trials 23(6):728–756PubMedCrossRefGoogle Scholar
  21. 21.
    Pierce JP, Natarajan L, Caan BJ, Parker BA, Greenberg ER, Flatt SW, Rock CL, Kealey S, Al-Delaimy WK, Bardwell WA, Carlson RW, Emond JA, Faerber S, Gold EB, Hajek RA, Hollenbach K, Jones LA, Karanja N, Madlensky L, Marshall J, Newman VA, Ritenbaugh C, Thomson CA, Wasserman L, Stefanick ML (2007) Influence of a diet very high in vegetables, fruit, and fiber and low in fat on prognosis following treatment for breast cancer: the Women’s Healthy Eating and Living (WHEL) randomized trial. JAMA 298(3):289–298. doi: 10.1001/jama.298.3.289 PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Levine DW, Kaplan RM, Kripke DF, Bowen DJ, Naughton MJ, Shumaker SA (2003) Factor structure and measurement invariance of the Women’s Health Initiative Insomnia Rating Scale. Psychol Assess 15(2):123–136PubMedCrossRefGoogle Scholar
  23. 23.
    Levine DW, Kripke DF, Kaplan RM, Lewis MA, Naughton MJ, Bowen DJ, Shumaker SA (2003) Reliability and validity of the Women’s Health Initiative Insomnia Rating Scale. Psychol Assess 15(2):137–148PubMedCrossRefGoogle Scholar
  24. 24.
    Levine DW, Dailey ME, Rockhill B, Tipping D, Naughton MJ, Shumaker SA (2005) Validation of the Women’s Health Initiative Insomnia Rating Scale in a multicenter controlled clinical trial. Psychosom Med 67(1):98–104. doi: 10.1097/01.psy.0000151743.58067.f0 PubMedCrossRefGoogle Scholar
  25. 25.
    Patterson RE, Flatt SW, Saquib N, Rock CL, Caan BJ, Parker BA, Laughlin GA, Erickson K, Thomson CA, Bardwell WA, Hajek RA, Pierce JP (2010) Medical comorbidities predict mortality in women with a history of early stage breast cancer. Breast Cancer Res Treat 122(3):859–865. doi: 10.1007/s10549-010-0732-3 PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Charlson ME, Pompei P, Ales KL, MacKenzie CR (1987) A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 40(5):373–383PubMedCrossRefGoogle Scholar
  27. 27.
    Ware JE Jr, Sherbourne CD (1992) The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care 30(6):473–483PubMedCrossRefGoogle Scholar
  28. 28.
    Goodwin PJ, Black JT, Bordeleau LJ, Ganz PA (2003) Health-related quality-of-life measurement in randomized clinical trials in breast cancer–taking stock. J Natl Cancer Inst 95(4):263–281PubMedCrossRefGoogle Scholar
  29. 29.
    Kosinski M, Keller SD, Hatoum HT, Kong SX, Ware JE, Jr (1999) The SF-36 Health Survey as a generic outcome measure in clinical trials of patients with osteoarthritis and rheumatoid arthritis: tests of data quality, scaling assumptions and score reliability. Medical care 37(5 Suppl):MS10–MS22PubMedGoogle Scholar
  30. 30.
    Ware JE Jr, Gandek B (1998) Overview of the SF-36 health survey and the international quality of life assessment (IQOLA) project. J Clin Epidemiol 51(11):903–912PubMedCrossRefGoogle Scholar
  31. 31.
    Hirshkowitz M, Whiton K, Albert SM, Alessi C, Bruni O, DonCarlos L, Hazen N, Herman J, Hillard PJA, Katz ES, Kheirandish-Gozal L, Neubauer DN, O’Donnell AE, Ohayon M, Peever J, Rawding R, Sachdeva RC, Setters B, Vitiello MV, Ware JC (2015) National sleep foundation’s updated sleep duration recommendations: final report. Sleep Health 1(14):233–243. doi: 10.1016/j.sleh.2015.10.004 CrossRefGoogle Scholar
  32. 32.
    Anderson PK, Gill RD (1982) Cox’s regression model for counting processes: a large sample study. Ann Stat 10(4):1100–1120. doi: 10.1214/aos/1176345976 CrossRefGoogle Scholar
  33. 33.
    Tucker AM, Dinges DF, Van Dongen HP (2007) Trait interindividual differences in the sleep physiology of healthy young adults. J Sleep Res 16(2):170–180. doi: 10.1111/j.1365-2869.2007.00594.x PubMedCrossRefGoogle Scholar
  34. 34.
    Aeschbach D, Sher L, Postolache TT, Matthews JR, Jackson MA, Wehr TA (2003) A longer biological night in long sleepers than in short sleepers. J Clin Endocrinol Metab 88(1):26–30. doi: 10.1210/jc.2002-020827 PubMedCrossRefGoogle Scholar
  35. 35.
    Clinton JM, Davis CJ, Zielinski MR, Jewett KA, Krueger JM (2011) Biochemical regulation of sleep and sleep biomarkers. J Clin Sleep Med 7(5 Suppl):S38–S42. doi: 10.5664/JCSM.1360 PubMedPubMedCentralGoogle Scholar
  36. 36.
    Krueger JM (2008) The role of cytokines in sleep regulation. Curr Pharm Des 14(32):3408–3416PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Krueger JM, Takahashi ST, Kapas L, Bredow S, Roky R, Fang J, Floyd R, Renegar KB, Guha-Thakurta N, Novitsky S, Obar FJ (1995) Cytokines in sleep regulation. Adv Neuroimmunol 5:171–188PubMedCrossRefGoogle Scholar
  38. 38.
    Villasenor A, Flatt SW, Marinac C, Natarajan L, Pierce JP, Patterson RE (2014) Postdiagnosis C-reactive protein and breast cancer survivorship: findings from the WHEL study. Cancer Epidemiol Biomark Prev 23(1):189–199. doi: 10.1158/1055-9965.EPI-13-0852 CrossRefGoogle Scholar
  39. 39.
    Reynold AM, Bowles ER, Saxena A, Fayad R, Youngstedt SD (2014) Negative Effects of Time in Bed Extension: a Pilot Study. J Sleep Med Disord 1(1):1Google Scholar
  40. 40.
    Bardwell WA, Natarajan L, Dimsdale JE, Rock CL, Mortimer JE, Hollenbach K, Pierce JP (2006) Objective cancer-related variables are not associated with depressive symptoms in women treated for early-stage breast cancer. J Clin Oncol 24(16):2420–2427. doi: 10.1200/JCO.2005.02.0081 PubMedCrossRefGoogle Scholar
  41. 41.
    Giese-Davis J, Collie K, Rancourt KM, Neri E, Kraemer HC, Spiegel D (2011) Decrease in depression symptoms is associated with longer survival in patients with metastatic breast cancer: a secondary analysis. J Clin Oncol 29(4):413–420. doi: 10.1200/JCO.2010.28.4455 PubMedCrossRefGoogle Scholar
  42. 42.
    Suppli NP, Johansen C, Kessing LV, Toender A, Kroman N, Ewertz M, Dalton SO (2016) Survival after early-stage breast cancer of women previously treated for depression: a nationwide Danish cohort study. J Clin Oncol. doi: 10.1200/JCO.2016.68.8358 PubMedGoogle Scholar
  43. 43.
    Musselman DL, Miller AH, Porter MR, Manatunga A, Gao F, Penna S, Pearce BD, Landry J, Glover S, McDaniel JS, Nemeroff CB (2001) Higher than normal plasma interleukin-6 concentrations in cancer patients with depression: preliminary findings. Am J Psychiatry 158(8):1252–1257. doi: 10.1176/appi.ajp.158.8.1252 PubMedCrossRefGoogle Scholar
  44. 44.
    Sephton SE, Dhabhar FS, Keuroghlian AS, Giese-Davis J, McEwen BS, Ionan AC, Spiegel D (2009) Depression, cortisol, and suppressed cell-mediated immunity in metastatic breast cancer. Brain Behav Immun 23(8):1148–1155. doi: 10.1016/j.bbi.2009.07.007 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Catherine R. Marinac
    • 1
    • 2
    • 3
  • Sandahl H. Nelson
    • 3
    • 4
    • 5
  • Shirley W. Flatt
    • 4
  • Loki Natarajan
    • 3
    • 4
  • John P. Pierce
    • 3
    • 4
  • Ruth E. Patterson
    • 3
    • 4
  1. 1.Dana-Farber Cancer InstituteBostonUSA
  2. 2.Harvard TH Chan School of Public HealthBostonUSA
  3. 3.Department of Family Medicine and Public HealthUniversity of California, San DiegoLa JollaUSA
  4. 4.Moores Cancer Center University of California, San DiegoLa JollaUSA
  5. 5.Graduate School of Public HealthSan Diego State UniversitySan DiegoUSA

Personalised recommendations