Skip to main content

Advertisement

Log in

Nausea and disturbed sleep as predictors of cancer-related fatigue in breast cancer patients: a multicenter NCORP study

  • Original Article
  • Published:
Supportive Care in Cancer Aims and scope Submit manuscript

Abstract

Purpose

Cancer-related fatigue (CRF) is a prevalent and distressing side effect of cancer and its treatment that remains inadequately understood and poorly managed. A better understanding of the factors contributing to CRF could result in more effective strategies for the prevention and treatment of CRF. The objectives of this study were to examine the prevalence, severity, and potential predictors for the early onset of CRF after chemotherapy cycle 1 in breast cancer patients.

Methods

We report on a secondary data analysis of 548 female breast cancer patients from a phase III multi-center randomized controlled trial examining antiemetic efficacy. CRF was assessed by the Brief Fatigue Inventory at pre- and post-chemotherapy cycle 1 as well as by the four-day diary.

Results

The prevalence of clinically relevant post-CRF was 75%. Linear regression showed that pre-treatment CRF, greater nausea, disturbed sleep, and younger age were significant risk factors for post-CRF (adjusted R2 = 0.39; P < 0.0001). Path modeling showed that nausea severity influenced post-CRF both directly and indirectly by influencing disturbed sleep. Similarly, pre-treatment CRF influenced post-CRF directly as well as indirectly through both nausea severity and disturbed sleep. Pearson correlations showed that changes in CRF over time were significantly correlated with concurrent changes in nausea severity (r = 0.41; P < 0.0001) and in disturbed sleep (r = 0.20; P < 0.0001).

Conclusion

This study showed a high prevalence (75%) of clinically relevant CRF in breast cancer patients following their initial chemotherapy, and that nausea severity, disturbed sleep, pre-treatment CRF, and age were significant predictors of symptom.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. American Cancer Society (2016) Cancer facts & figures 2016. American Cancer Society, Atlanta

    Google Scholar 

  2. Berger AM, Gerber LH, Mayer DK (2012) Cancer-related fatigue: implications for breast cancer survivors. Cancer 118(8 Suppl):2261–2269. doi:10.1002/cncr.27475

    Article  PubMed  Google Scholar 

  3. NCCN Cancer-Related Fatigue Panel: National Comprehensive Cancer Network (2016) Clinical practice guidelines in oncology. Cancer-Related Fatigue, version 1, pp 1–56

  4. Glaus A, Crow R, Hammond S (1996) A qualitative study to explore the concept of fatigue/tiredness in cancer patients and in healthy individuals. Support Care Cancer 4(2):82–96

    Article  CAS  PubMed  Google Scholar 

  5. Schmidt ME, Chang-Claude J, Vrieling A, Heinz J, Flesch-Janys D, Steindorf K (2012) Fatigue and quality of life in breast cancer survivors: temporal courses and long-term pattern. Journal of cancer survivorship : research and practice 6(1):11–19. doi:10.1007/s11764-011-0197-3

    Article  Google Scholar 

  6. Jacobsen PB, Hann DM, Azzarello LM, Horton J, Balducci L, Lyman GH (1999) Fatigue in women receiving adjuvant chemotherapy for breast cancer: characteristics, course, and correlates. J Pain Symptom Manag 18(4):233–242

    Article  CAS  Google Scholar 

  7. Greene D, Nail LM, Fieler VK, Dudgeon D, Jones LS (1994) A comparison of patient-reported side effects among three chemotherapy regimens for breast cancer. Cancer Pract 2(1):57–62

    CAS  PubMed  Google Scholar 

  8. Andrykowski MA, Schmidt JE, Salsman JM, Beacham AO, Jacobsen PB (2005) Use of a case definition approach to identify cancer-related fatigue in women undergoing adjuvant therapy for breast cancer. J Clin Oncol 23(27):6613–6622. doi:10.1200/JCO.2005.07.024

    Article  PubMed  Google Scholar 

  9. Lawrence DP, Kupelnick B, Miller K, Devine D, Lau J (2004) Evidence report on the occurrence, assessment, and treatment of fatigue in cancer patients. J Natl Cancer Inst Monogr 32:40–50. doi:10.1093/jncimonographs/lgh027

    Article  Google Scholar 

  10. Borneman T, Koczywas M, Sun VC, Piper BF, Uman G, Ferrell B (2010) Reducing patient barriers to pain and fatigue management. J Pain Symptom Manag 39(3):486–501. doi:10.1016/j.jpainsymman.2009.08.007

    Article  Google Scholar 

  11. Hofman M, Ryan JL, Figueroa-Moseley CD, Jean-Pierre P, Morrow GR (2007) Cancer-related fatigue: the scale of the problem. Oncologist 12(Suppl 1):4–10. doi:10.1634/theoncologist.12-S1-4

    Article  PubMed  Google Scholar 

  12. Scott JA, Lasch KE, Barsevick AM, Piault-Louis E (2011) Patients’ experiences with cancer-related fatigue: a review and synthesis of qualitative research. Oncol Nurs Forum 38(3):E191–E203. doi:10.1188/11.ONF.E191-E203

    Article  PubMed  Google Scholar 

  13. Groenvold M, Petersen MA, Idler E, Bjorner JB, Fayers PM, Mouridsen HT (2007) Psychological distress and fatigue predicted recurrence and survival in primary breast cancer patients. Breast Cancer Res Treat 105(2):209–219. doi:10.1007/s10549-006-9447-x

    Article  PubMed  Google Scholar 

  14. Curt GA, Breitbart W, Cella D, Groopman JE, Horning SJ, Itri LM, Johnson DH, Miaskowski C, Scherr SL, Portenoy RK, Vogelzang NJ (2000) Impact of cancer-related fatigue on the lives of patients: new findings from the fatigue coalition. Oncologist 5(5):353–360

    Article  CAS  PubMed  Google Scholar 

  15. Wang XS (2008) Pathophysiology of cancer-related fatigue. Clin J Oncol Nurs 12(5 Suppl):11–20. doi:10.1188/08.CJON.S2.11-20

    Article  PubMed  PubMed Central  Google Scholar 

  16. Wang XS, Woodruff JF (2015) Cancer-related and treatment-related fatigue. Gynecol Oncol 136(3):446–452. doi:10.1016/j.ygyno.2014.10.013

    Article  PubMed  Google Scholar 

  17. Roscoe JA, Heckler CE, Morrow GR, Mohile SG, Dakhil SR, Wade JL, Kuebler JP (2012) Prevention of delayed nausea: a University of Rochester Cancer Center Community Clinical Oncology Program study of patients receiving chemotherapy. J Clin Oncol 30(27):3389–3395. doi:10.1200/JCO.2011.39.8123

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Mendoza TR, Wang XS, Cleeland CS, Morrissey M, Johnson BA, Wendt JK, Huber SL (1999) The rapid assessment of fatigue severity in cancer patients: use of the brief fatigue inventory. Cancer 85(5):1186–1196

    Article  CAS  PubMed  Google Scholar 

  19. Burish TG, Carey MP, Krozely MG, Greco FA (1987) Conditioned side effects induced by cancer chemotherapy: prevention through behavioral treatment. J Consult Clin Psychol 55(1):42–48

    Article  CAS  PubMed  Google Scholar 

  20. Carey MP, Burish TG (1988) Etiology and treatment of the psychological side effects associated with cancer chemotherapy: a critical review and discussion. Psychol Bull 104(3):307–325

    Article  CAS  PubMed  Google Scholar 

  21. Gilliam LA, St Clair DK (2011) Chemotherapy-induced weakness and fatigue in skeletal muscle: the role of oxidative stress. Antioxid Redox Signal 15(9):2543–2563. doi:10.1089/ars.2011.3965

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. NCCN Breast Cancer: National Comprehensive Cancer Network (2016) Clinical practice guidelines in oncology. Breast Cancer, version 2, pp 1–202

  23. Minton O, Alexander S, Stone PC (2012) Identification of factors associated with cancer related fatigue syndrome in disease-free breast cancer patients after completing primary treatment. Breast Cancer Res Treat 136(2):513–520. doi:10.1007/s10549-012-2284-1

    Article  PubMed  Google Scholar 

  24. Kim SH, Son BH, Hwang SY, Han W, Yang JH, Lee S, Yun YH (2008) Fatigue and depression in disease-free breast cancer survivors: prevalence, correlates, and association with quality of life. J Pain Symptom Manag 35(6):644–655. doi:10.1016/j.jpainsymman.2007.08.012

    Article  Google Scholar 

  25. Garabeli Cavalli Kluthcovsky AC, Urbanetz AA, de Carvalho DS, Pereira Maluf EM, Schlickmann Sylvestre GC, Bonatto Hatschbach SB (2012) Fatigue after treatment in breast cancer survivors: prevalence, determinants and impact on health-related quality of life. Support Care Cancer 20(8):1901–1909. doi:10.1007/s00520-011-1293-7

    Article  PubMed  Google Scholar 

  26. Paiva CE, Paiva BS (2013) Prevalence, predictors, and prognostic impact of fatigue among Brazilian outpatients with advanced cancers. Support Care Cancer 21(4):1053–1060. doi:10.1007/s00520-012-1625-2

    Article  PubMed  Google Scholar 

  27. Stobaus N, Muller MJ, Kupferling S, Schulzke JD, Norman K (2015) Low recent protein intake predicts cancer-related fatigue and increased mortality in patients with advanced tumor disease undergoing chemotherapy. Nutr Cancer 67(5):818–824. doi:10.1080/01635581.2015.1040520

    Article  CAS  PubMed  Google Scholar 

  28. Alexander S, Minton O, Andrews P, Stone P (2009) A comparison of the characteristics of disease-free breast cancer survivors with or without cancer-related fatigue syndrome. Eur J Cancer 45(3):384–392. doi:10.1016/j.ejca.2008.09.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Liu L, Rissling M, Natarajan L, Fiorentino L, Mills PJ, Dimsdale JE, Sadler GR, Parker BA, Ancoli-Israel S (2012) The longitudinal relationship between fatigue and sleep in breast cancer patients undergoing chemotherapy. Sleep 35(2):237–245. doi:10.5665/sleep.1630

    Article  PubMed  PubMed Central  Google Scholar 

  30. Goedendorp MM, Gielissen MF, Verhagen CA, Bleijenberg G (2013) Development of fatigue in cancer survivors: a prospective follow-up study from diagnosis into the year after treatment. J Pain Symptom Manag 45(2):213–222. doi:10.1016/j.jpainsymman.2012.02.009

    Article  Google Scholar 

  31. Banthia R, Malcarne VL, Ko CM, Varni JW, Sadler GR (2009) Fatigued breast cancer survivors: the role of sleep quality, depressed mood, stage and age. Psychol Health 24(8):965–980. doi:10.1080/08870440802110831

    Article  PubMed  PubMed Central  Google Scholar 

  32. Roscoe JA, Morrow GR, Hickok JT, Bushunow P, Matteson S, Rakita D, Andrews PL (2002) Temporal interrelationships among fatigue, circadian rhythm and depression in breast cancer patients undergoing chemotherapy treatment. Support Care Cancer 10(4):329–336. doi:10.1007/s00520-001-0317-0

    Article  PubMed  Google Scholar 

  33. Roscoe JA, Kaufman ME, Matteson-Rusby SE, Palesh OG, Ryan JL, Kohli S, Perlis ML, Morrow GR (2007) Cancer-related fatigue and sleep disorders. Oncologist 12(Suppl 1):35–42. doi:10.1634/theoncologist.12-S1-35

    Article  PubMed  Google Scholar 

  34. Pertl MM, Hevey D, Collier S, Lambe K, O’Dwyer AM (2014) Predictors of fatigue in cancer patients before and after chemotherapy. J Health Psychol 19(6):699–710. doi:10.1177/1359105313477675

    Article  PubMed  Google Scholar 

  35. Goedendorp MM, Gielissen MF, Verhagen CA, Peters ME, Bleijenberg G (2008) Severe fatigue and related factors in cancer patients before the initiation of treatment. Br J Cancer 99(9):1408–1414. doi:10.1038/sj.bjc.6604739

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Dhruva A, Dodd M, Paul SM, Cooper BA, Lee K, West C, Aouizerat BE, Swift PS, Wara W, Miaskowski C (2010) Trajectories of fatigue in patients with breast cancer before, during, and after radiation therapy. Cancer Nurs 33(3):201–212. doi:10.1097/NCC.0b013e3181c75f2a

    Article  PubMed  PubMed Central  Google Scholar 

  37. Singer S, Kuhnt S, Zwerenz R, Eckert K, Hofmeister D, Dietz A, Giesinger J, Hauss J, Papsdorf K, Briest S, Brown A (2011) Age- and sex-standardised prevalence rates of fatigue in a large hospital-based sample of cancer patients. Br J Cancer 105(3):445–451. doi:10.1038/bjc.2011.251

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Soltow D, Given BA, Given CW (2010) Relationship between age and symptoms of pain and fatigue in adults undergoing treatment for cancer. Cancer Nurs 33(4):296–303. doi:10.1097/NCC.0b013e3181ce5a1a

    Article  PubMed  Google Scholar 

  39. Hamre H, Zeller B, Kanellopoulos A, Ruud E, Fossa SD, Loge JH, Aukrust P, Halvorsen B, Mollnes TE, Kiserud CE (2013) Serum cytokines and chronic fatigue in adults surviving after childhood leukemia and lymphoma. Brain Behav Immun 30:80–87. doi:10.1016/j.bbi.2013.01.006

    Article  CAS  PubMed  Google Scholar 

  40. Butt Z, Rao AV, Lai JS, Abernethy AP, Rosenbloom SK, Cella D (2010) Age-associated differences in fatigue among patients with cancer. J Pain Symptom Manag 40(2):217–223. doi:10.1016/j.jpainsymman.2009.12.016

    Article  Google Scholar 

  41. Booth CM, Clemons M, Dranitsaris G, Joy A, Young S, Callaghan W, Trudeau M, Petrella T (2007) Chemotherapy-induced nausea and vomiting in breast cancer patients: a prospective observational study. J Support Oncol 5(8):374–380

    PubMed  Google Scholar 

  42. Fiorentino L, Ancoli-Israel S (2006) Insomnia and its treatment in women with breast cancer. Sleep Med Rev 10(6):419–429. doi:10.1016/j.smrv.2006.03.005

    Article  PubMed  PubMed Central  Google Scholar 

  43. Savard J, Villa J, Ivers H, Simard S, Morin CM (2009) Prevalence, natural course, and risk factors of insomnia comorbid with cancer over a 2-month period. J Clin Oncol 27(31):5233–5239. doi:10.1200/JCO.2008.21.6333

    Article  PubMed  Google Scholar 

  44. Heckler CE, Garland SN, Peoples AR, Perlis ML, Shayne M, Morrow GR, Kamen C, Hoefler J, Roscoe JA (2016) Cognitive behavioral therapy for insomnia, but not armodafinil, improves fatigue in cancer survivors with insomnia: a randomized placebo-controlled trial. Support Care Cancer 24(5):2059–2066. doi:10.1007/s00520-015-2996-y

    Article  PubMed  Google Scholar 

  45. Ryan JL, Heckler CE, Roscoe JA, Dakhil SR, Kirshner J, Flynn PJ, Hickok JT, Morrow GR (2012) Ginger (Zingiber officinale) reduces acute chemotherapy-induced nausea: a URCC CCOP study of 576 patients. Support Care Cancer 20(7):1479–1489. doi:10.1007/s00520-011-1236-3

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This study is supported by NCI grants U10 CA37420, R25 CA102618, and UG1 CA189961. Study medication was provided by MGI Pharma, Bloomington, MN.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Anita R. Peoples.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest. Dr. Roscoe has full control of the primary data and agrees to allow the journal to review the data if requested.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee 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.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Peoples, A.R., Roscoe, J.A., Block, R.C. et al. Nausea and disturbed sleep as predictors of cancer-related fatigue in breast cancer patients: a multicenter NCORP study. Support Care Cancer 25, 1271–1278 (2017). https://doi.org/10.1007/s00520-016-3520-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00520-016-3520-8

Keywords

Navigation