Supportive Care in Cancer

, Volume 22, Issue 9, pp 2535–2545 | Cite as

Sleep, fatigue, depression, and circadian activity rhythms in women with breast cancer before and after treatment: a 1-year longitudinal study

  • Sonia Ancoli-IsraelEmail author
  • Lianqi Liu
  • Michelle Rissling
  • Loki Natarajan
  • Ariel B. Neikrug
  • Barton W. Palmer
  • Paul J. Mills
  • Barbara A. Parker
  • Georgia Robins Sadler
  • Jeanne Maglione
Original Article



Sleep disturbance, fatigue and depression are common complaints in patients with cancer, and often contribute to worse quality of life (QoL). Circadian activity rhythms (CARs) are often disrupted in cancer patients. These symptoms worsen during treatment, but less is known about their long-term trajectory.


Sixty-eight women with stage I-III breast cancer (BC) scheduled to receive ≥4 cycles of chemotherapy, and age-, ethnicity-, and education-matched normal, cancer-free controls (NC) participated. Sleep was measured with actigraphy (nocturnal total sleep time [nocturnal TST] and daytime total nap time [NAPTIME]) and with the Pittsburgh Sleep Quality Index (PSQI); fatigue with the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF); depression with the Center of Epidemiological Studies-Depression (CES-D). CARs were derived from actigraphy. Several measures of QoL were administered. Data were collected at three time points: before (baseline), end of cycle 4 (cycle 4), and 1 year post-chemotherapy (1 year).


Compared to NC, BC had longer NAPTIME, worse sleep quality, more fatigue, more depressive symptoms, more disrupted CARs, and worse QoL at baseline (all p values <0.05). At cycle 4, BC showed worse sleep, increased fatigue, more depressive symptoms, and more disrupted CARs compared to their own baseline levels and to NC (all p values <0.05). By 1 year, BC’s fatigue, depressive symptoms, and QoL returned to baseline levels but were still worse than those of NC, while NAPTIME and CARs did not differ from NC’s.


Additional research is needed to determine if beginning treatment of these symptoms before the start of chemotherapy will minimize symptom severity over time.


Sleep disturbance Fatigue Depression Circadian activity rhythms Quality of life Breast cancer 



This study was supported by the National Cancer Institute (CA112035 and P30 CA023100), the UCSD Clinical and Translational Research Institute (UL1RR031980), and the Department of Veterans Affairs San Diego Center of Excellence for Stress and Mental Health (CESAMH). The authors would like to thank all women who participated in this study either as patients or controls. The study was funded by NIH

Conflict of interest

The corresponding author has full control of all primary data and agrees to allow the Journal to review the data if requested.


  1. 1.
    Fernandes R, Stone P, Andrews P, Morgan R, Sharma S (2006) Comparison between fatigue, sleep disturbance, and circadian rhythm in cancer inpatients and healthy volunteers: evaluation of diagnostic criteria for cancer-related fatigue. J Pain Symptom Manage 32:245–254PubMedCrossRefGoogle Scholar
  2. 2.
    Esther Kim JE, Dodd MJ, Aouizerat BE, Jahan T, Miaskowski C (2009) A review of the prevalence and impact of multiple symptoms in oncology patients. J Pain Symptom Manage 37:715–736PubMedCrossRefGoogle Scholar
  3. 3.
    Ancoli-Israel S, Liu L, Marler M, Parker BA, Jones V, Robins Sadler G, Dimsdale JE, Cohen-Zion M, Fiorentino L (2006) Fatigue, sleep and circadian rhythms prior to chemotherapy for breast cancer. Support Care Cancer 14:201–209PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Berger AM, Farr LA, Kuhn BR, Fischer P, Agrawal S (2007) Values of sleep/wake, activity/rest, circadian rhythms, and fatigue prior to adjuvant breast cancer chemotherapy. J Pain Symptom Manage 33:398–409PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Miaskowski C, Lee K, Dunn L, Dodd M, Aouizerat BE, West C, Paul SM, Cooper B, Wara W, Swift P (2011) Sleep-wake circadian activity rhythm parameters and fatigue in oncology patients before the initiation of radiation therapy. Cancer Nurs 34:255–268PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Bower JE, Ganz PA, Desmond KA, Rowland JH, Meyerowitz BE, Belin TR (2000) Fatigue in breast cancer survivors: occurrence, correlates, and impact on quality of life. J Clin Oncol 18:743–753PubMedGoogle Scholar
  7. 7.
    Byar KL, Berger AM, Bakken SL, Cetak MA (2006) Impact of adjuvant breast cancer chemotherapy on fatigue, other symptoms, and quality of life. Oncol Nurs Forum 33:E18–E26PubMedCrossRefGoogle Scholar
  8. 8.
    Dodd MJ, Cho MH, Cooper BA, Miaskowski C (2010) The effect of symptom clusters on functional status and quality of life in women with breast cancer. Eur J Oncol Nurs 14:101–110PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Sandadi S, Frasure HE, Broderick MJ, Waggoner SE, Miller JA, von Gruenigen VE (2011) The effect of sleep disturbance on quality of life in women with ovarian cancer. Gynecol Oncol 123:351–355PubMedCrossRefGoogle Scholar
  10. 10.
    Fiorentino L, Ancoli-Israel S (2006) Insomnia and its treatment in women with breast cancer. Sleep Med Rev 10:419–429PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Savard J, Simard S, Blanchet J, Ivers H, Morin CM (2001) Prevalence, clinical characteristics, and risk factors for insomnia in the context of breast cancer. Sleep 24:583–590PubMedGoogle Scholar
  12. 12.
    Liu L, Marler M, Parker BA, Jones V, Johnson S, Cohen-Zion M, Fiorentino L, Sadler GR, Ancoli-Israel S (2005) The relationship between fatigue and light exposure during chemotherapy. Support Care Cancer 13:1010–1017PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Liu L, Fiorentino L, Natarajan L, Parker BA, Mills PJ, Sadler GR, Dimsdale JE, Rissling M, He F, Ancoli-Israel S (2009) Pre-treatment symptom cluster in breast cancer patients is associated with worse sleep, fatigue and depression during chemotherapy. Psycho-oncology 18:187–194PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Hofman M, Ryan JL, Figueroa-Moseley CD, Jean-Pierre P, Morrow GR (2007) Cancer-related fatigue: the scale of the problem. Oncologist 12(1):4–10, 4-10PubMedCrossRefGoogle Scholar
  15. 15.
    Berger AM, Gerber LH, Mayer DK (2012) Cancer-related fatigue: implications for breast cancer survivors. Cancer 118:2261–2269PubMedCrossRefGoogle Scholar
  16. 16.
    Morrow GR, Andrews PLR, Hickok JT, Roscoe JA, Matteson S (2002) Fatigue associated with cancer and its treatment. Support Care Cancer 10:389–398PubMedCrossRefGoogle Scholar
  17. 17.
    Trudel-Fitzgerald C, Savard J, Ivers H (2013) Which symptoms come first? Exploration of temporal relationships between cancer-related symptoms over an 18-month period. Ann Behav Med 45:329–337PubMedCrossRefGoogle Scholar
  18. 18.
    So WK, Marsh G, Ling WM, Leung FY, Lo JC, Yeung M, Li GK (2009) The symptom cluster of fatigue, pain, anxiety, and depression and the effect on the quality of life of women receiving treatment for breast cancer: a multicenter study. Oncol Nurs Forum 36:E205–E214PubMedCrossRefGoogle Scholar
  19. 19.
    Massie MJ (2004) Prevalence of depression in patients with cancer. J Natl Cancer Inst Monogr 2004:57–71CrossRefGoogle Scholar
  20. 20.
    Gehrman PR, Marler M, Martin JL, Shochat T, Corey-Bloom J, Ancoli-Israel S (2004) The timing of activity rhythms in patients with dementia is related to survival. Journal of Gerontology: Medical Sciences 59A:1050–1055Google Scholar
  21. 21.
    Paudel M, Taylor BC, Ancoli-Israel S, Blackwell T, Stone KL, Tranah G, Redline SS, Cummings SR, Ensrud KE, For the Osteoporotic Fractures in Men(MrOS) Study Group (2010) Rest/activity rhythms and mortality rates in older men: the MrOs sleep study. Chronobiol Int 27:363–377PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Tranah GJ, Blackwell TL, Ancoli-Israel S, Paudel M, Ensrud K, Cauley JA, Hillier TA, Cummings SR, Stone KL, For the SOF Research Group (2010) Circadian activity rhythms and mortality: the study of osteoporotic fractures. J Am Geriatr Soc 58:282–291PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Mormont MC, Waterhouse J, Bleuzen P, Giacchetti S, Jami A, Bogdan A, Touitou Y, Levi F (2000) Marked 24-h rest/activity rhythms are associated with better quality of life, better response and longer survival in patients with metastatic colorectal cancer and good performance status. Clin Cancer Res 6:3038–3045PubMedGoogle Scholar
  24. 24.
    Berger AM, Hertzog M, Geary CR, Fischer P, Farr L (2012) Circadian rhythms, symptoms, physical functioning, and body mass index in breast cancer survivors. J Cancer Surviv 6:305–314PubMedCrossRefGoogle Scholar
  25. 25.
    Savard J, Liu L, Natajaran L, Rissling M, Neikrug AB, He F, Dimsdale JE, Mills PJ, Parker BA, Sadler GR, Ancoli-Israel S (2009) Breast cancer patients have progressively impaired sleep-wake activity rhythms during chemotherapy. Sleep 32:1155–1160PubMedCentralPubMedGoogle Scholar
  26. 26.
    Bower JE, Ganz PA, Desmond KA, Rowland JH, Meyerowitz BE, Belin TR (2000) Fatigue in breast cancer survivors: occurrence, correlates, and impact on quality of life. J Clin Oncol 18:743–753PubMedGoogle Scholar
  27. 27.
    Broeckel J, Jacobsen PB, Horton J, Balducci L, Lyman GH (1998) Characteristics and correlates of fatigue after adjuvant chemotherapy for breast cancer. Journal of Cinical Oncology 16:1689–1696Google Scholar
  28. 28.
    Pockaj BA, Degnim AC, Boughey JC, Gray RJ, McLaughlin SA, Dueck AC, Perez EA, Halyard MY, Frost MH, Cheville AL (2009) Quality of life after breast cancer surgery: what have we learned and where should we go next. J Surg Oncol 99:447–455PubMedCrossRefGoogle Scholar
  29. 29.
    Trentham-Dietz A, Sprague BL, Klein R, Klein BE, Cruickshanks KJ, Fryback DG, Hampton JM (2008) Health-related quality of life before and after a breast cancer diagnosis. Breast Cancer Res Treat 109:379–387PubMedCrossRefGoogle Scholar
  30. 30.
    Ancoli-Israel S, Cole R, Alessi CA, Chambers M, Moorcroft WH, Pollak C (2003) The role of actigraphy in the study of sleep and circadian rhythms. Sleep 26:342–392PubMedGoogle Scholar
  31. 31.
    Liu L, Rissling MB, Neikrug AB, Fiorentino L, Natarajan L, Faierman M, Sadler GR, Dimsdale JE, Mills PJ, Parker BA, Ancoli-Israel S (2013) Fatigue and circadian activity rhythms in breast cancer patients before and after chemotherapy: a controlled study. Fatigue: Biomedicine, Health & Behavior 1:12–26Google Scholar
  32. 32.
    Buysse DJ, Reynolds CRI, Monk TH, Hoch CC, Yeager AL, Kupfer DJ (1991) Quantification of subjective sleep quality in healthy elderly men and women using the Pittsburgh Sleep Quality Index (PSQI). Sleep 14(4):331–338PubMedGoogle Scholar
  33. 33.
    Buysse DJ, Reynolds CFI, Monk TH, Berman SR, Kupfer DJ (1989) The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res 28(2):193–213PubMedCrossRefGoogle Scholar
  34. 34.
    Stein KD, Martin SC, Hann DM, Jacobsen PB (1998) A multidimensional measure of fatigue for use with cancer patients. Cancer Pract 6:143–152PubMedCrossRefGoogle Scholar
  35. 35.
    Stein KD, Jacobsen PB, Blanchard CM, Thors C (2004) Further validation of the multidimensional fatigue symptom inventory-short form. J Pain Symptom Manage 27:14–23PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Radloff LS (1977) The CES-D scale: A self-report depression scale for research in the general population. Applied Psychol Measurement 1:385–401CrossRefGoogle Scholar
  37. 37.
    Marler MR, Martin JL, Gehrman PR, Ancoli-Israel S (2006) The sigmoidally-transformed cosine curve: a mathematical model for circadian rhythms with symmetric non-sinusoidal shapes. Stat Med 25:3893–3904PubMedCrossRefGoogle Scholar
  38. 38.
    Weaver TE, Laizner AM, Evans LK, Maislin G, Chugh DK, Lyon K, Smith PL, Schwartz AR, Redline S, Pack AI, Dinges DF (1997) An instrument to measure functional status outcome for disorders of excessive sleepiness. Sleep 20:835–843PubMedGoogle Scholar
  39. 39.
    Ware JE, Kosinski M, Gandek B (2002) SF-36 Health survey: manual & interpretation guide. QualityMetric Incorporated, Lincoln, RIGoogle Scholar
  40. 40.
    Diggle PJ, Liang KY, Zeger SL (1994) Analysis of longitudinal data. Oxford University Press, New York, NYGoogle Scholar
  41. 41.
    Savard J, Morin CM (2001) Insomnia in the context of cancer: a review of a neglected problem. J Clin Oncol 19:895–908PubMedGoogle Scholar
  42. 42.
    Roscoe JA, Morrow GR, Hickok JT, Bushunow P, Matteson S, Rakita D, Andrews PLR (2002) Temporal interrelationships among fatigue, circadian rhythm and depression in breast cancer patients undergoing chemotherapy treatment. Support Care Cancer 10:329–336PubMedCrossRefGoogle Scholar
  43. 43.
    Berger AM, Wielgus K, Hertzog M, Fischer P, Farr L (2009) Patterns of circadian activity rhythms and their relationships with fatigue and anxiety/depression in women treated with breast cancer adjuvant chemotherapy. Support Care Cancer 18(1):105–114PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Sonia Ancoli-Israel
    • 1
    • 2
    • 5
    • 6
    • 8
    Email author
  • Lianqi Liu
    • 1
    • 7
    • 8
  • Michelle Rissling
    • 1
    • 5
  • Loki Natarajan
    • 3
    • 5
    • 6
  • Ariel B. Neikrug
    • 1
    • 5
  • Barton W. Palmer
    • 1
    • 5
  • Paul J. Mills
    • 1
    • 5
  • Barbara A. Parker
    • 2
    • 6
  • Georgia Robins Sadler
    • 4
    • 6
  • Jeanne Maglione
    • 1
  1. 1.Department of PsychiatryUniversity of California, San DiegoLa JollaUSA
  2. 2.Department of MedicineUniversity of California, San DiegoLa JollaUSA
  3. 3.Department of Family and Preventive MedicineUniversity of California, San DiegoLa JollaUSA
  4. 4.Department of SurgeryUniversity of California, San DiegoLa JollaUSA
  5. 5.SDSU/UCSD Joint Doctoral Program in Clinical PsychologySan DiegoUSA
  6. 6.UCSD Moores Cancer CenterLa JollaUSA
  7. 7.Veterans Affairs San Diego Healthcare SystemSan DiegoUSA
  8. 8.VA Center of Excellence for Stress and Mental HealthSan DiegoUSA

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