Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Cancer-related fatigue—mechanisms, risk factors, and treatments

Key Points

  • Fatigue is the most common adverse effect of cancer

  • Inflammation is a key mechanism of cancer-related fatigue

  • Host factors increase risk for fatigue in patients with cancer

  • Effective interventions include exercise and targeted psychological and mind–body treatments

Abstract

Fatigue is one of the most common adverse effects of cancer that might persist for years after treatment completion in otherwise healthy survivors. Cancer-related fatigue causes disruption in all aspects of quality of life and might be a risk factor of reduced survival. The prevalence and course of fatigue in patients with cancer have been well characterized and there is growing understanding of the underlying biological mechanisms. Inflammation seems to have a key role in fatigue before, during, and after cancer-treatment. However, there is a considerable variability in the presentation of cancer-related fatigue, much of which is not explained by disease-related or treatment-related characteristics, suggesting that host factors might be important in the development and persistence of this symptom. Indeed, longitudinal studies have identified genetic, biological, psychosocial, and behavioural risk factors associated with cancer-related fatigue. Although no current gold-standard treatment for fatigue is available, a variety of intervention approaches have shown beneficial effects in randomized controlled trials, including physical activity, psychosocial, mind–body, and pharmacological treatments. This Review describes the mechanisms, risk factors, and possible interventions for cancer-related fatigue, focusing on recent longitudinal studies and randomized trials that have targeted fatigued patients.

This is a preview of subscription content

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1: Mechanisms of cancer-related fatigue.

References

  1. Lawrence, D. P., Kupelnick, B., Miller, K., Devine, D. & Lau, J. Evidence report on the occurrence, assessment, and treatment of fatigue in cancer patients. J. Natl Cancer Inst. Monogr. 32, 40–50 (2004).

    Article  Google Scholar 

  2. Hickok, J. T. et al. Frequency, severity, clinical course, and correlates of fatigue in 372 patients during 5 weeks of radiotherapy for cancer. Cancer 104, 1772–1778 (2005).

    PubMed  Article  Google Scholar 

  3. Jacobsen, P. B. et al. Fatigue in women receiving adjuvant chemotherapy for breast cancer: characteristics, course, and correlates. J. Pain Symptom Manage. 18, 233–242 (1999).

    CAS  PubMed  Article  Google Scholar 

  4. Phillips, K. et al. Quality of life outcomes in patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors: a controlled comparison. Support. Care Cancer 21, 1097–1103 (2013).

    PubMed  Article  Google Scholar 

  5. Servaes, P., Verhagen, C. & Bleijenberg, G. Fatigue in cancer patients during and after treatment: prevalence, correlates and interventions. Eur. J. Cancer 38, 27–43 (2002).

    CAS  PubMed  Article  Google Scholar 

  6. Bower, J. E. et al. Fatigue in breast cancer survivors: occurrence, correlates, and impact on quality of life. J. Clin. Oncol. 18, 743–753 (2000).

    CAS  PubMed  Article  Google Scholar 

  7. Cella, D., Davis, K., Breitbart, W. & Curt, G. Cancer-related fatigue: prevalence of proposed diagnostic criteria in a United States sample of cancer survivors. J. Clin. Oncol. 19, 3385–3391 (2001).

    CAS  PubMed  Article  Google Scholar 

  8. Minton, O. & Stone, P. How common is fatigue in disease-free breast cancer survivors? A systematic review of the literature. Breast Cancer Res. Treat. 112, 5–13 (2008).

    CAS  PubMed  Article  Google Scholar 

  9. Bower, J. E. et al. Fatigue in long-term breast carcinoma survivors: a longitudinal investigation. Cancer 106, 751–758 (2006).

    PubMed  Article  Google Scholar 

  10. Curt, G. A. et al. Impact of cancer-related fatigue on the lives of patients: new findings from the Fatigue Coalition. Oncologist 5, 353–360 (2000).

    CAS  PubMed  Article  Google Scholar 

  11. Groenvold, M. et al. Psychological distress and fatigue predicted recurrence and survival in primary breast cancer patients. Breast Cancer Res. Treat. 105, 209–219 (2007).

    PubMed  Article  Google Scholar 

  12. Poulson, M. J. The art of oncology: when the tumor is not the target—not just tired. J. Clin. Oncol. 19, 4180–4181 (2001).

    CAS  PubMed  Article  Google Scholar 

  13. Braun, I. M., Greenberg, D. B. & Pirl, W. F. Evidenced-based report on the occurrence of fatigue in long-term cancer survivors. J. Natl Compr. Canc. Netw. 6, 347–54 (2008).

    PubMed  Article  Google Scholar 

  14. Vogelzang, N. J. et al. Patient, caregiver, and oncologist perceptions of cancer-related fatigue: results of a tripart assessment survey. The Fatigue Coalition. Semin. Haematol. 34, 4–12 (1997).

    CAS  Google Scholar 

  15. Mitchell, S. A. Cancer-related fatigue: state of the science. PM R 2, 364–383 (2010).

    PubMed  Article  Google Scholar 

  16. Donovan, K. A., Small, B. J., Andrykowski, M. A., Munster, P. & Jacobsen, P. B. Utility of a cognitive-behavioural model to predict fatigue following breast cancer treatment. Health Psychol. 26, 464–472 (2007).

    PubMed  PubMed Central  Article  Google Scholar 

  17. Barsevick, A., Frost, M., Zwinderman, A., Hall, P. & Halyard, M. I'm so tired: biological and genetic mechanisms of cancer-related fatigue. Qual. Life Res. 19, 1419–1427 (2010).

    PubMed  PubMed Central  Article  Google Scholar 

  18. Morrow, G. R., Andrews, P. L., Hickok, J. T., Roscoe, J. A. & Matteson, S. Fatigue associated with cancer and its treatment. Support. Care Cancer 10, 389–398 (2002).

    PubMed  Article  Google Scholar 

  19. Dantzer, R., O'Connor, J. C., Freund, G. G., Johnson, R. W. & Kelley, K. W. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat. Rev. Neurosci. 9, 46–56 (2008).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  20. Haroon, E., Raison, C. L. & Miller, A. H. Psychoneuroimmunology meets neuropsychopharmacology: translational implications of the impact of inflammation on behaviour. Neuropsychopharmacology 37, 137–162 (2012).

    CAS  PubMed  Article  Google Scholar 

  21. Miller, A. H., Ancoli-Israel, S., Bower, J. E., Capuron, L. & Irwin, M. R. Neuroendocrine-immune mechanisms of behavioural comorbidities in patients with cancer. J. Clin. Oncol. 26, 971–982 (2008).

    CAS  PubMed  Article  Google Scholar 

  22. Seruga, B., Zhang, H., Bernstein, L. J. & Tannock, I. F. Cytokines and their relationship to the symptoms and outcome of cancer. Nat. Rev. Cancer 8, 887–899 (2008).

    CAS  PubMed  Article  Google Scholar 

  23. Schaue, D., Kachikwu, E. L. & McBride, W. H. Cytokines in radiobiological responses: a review. Radiat. Res. 178, 505–523 (2012).

    PubMed  PubMed Central  Article  Google Scholar 

  24. Meyers, C. A., Albitar, M. & Estey, E. Cognitive impairment, fatigue, and cytokine levels in patients with acute myelogenous leukemia or myelodysplastic syndrome. Cancer 104, 788–793 (2005).

    CAS  PubMed  Article  Google Scholar 

  25. Clevenger, L. et al. Sleep disturbance, cytokines, and fatigue in women with ovarian cancer. Brain Behav. Immun. 26, 1037–1044 (2012).

    PubMed  PubMed Central  Article  Google Scholar 

  26. Lutgendorf, S. K. et al. Interleukin-6, cortisol, and depressive symptoms in ovarian cancer patients. J. Clin. Oncol. 26, 4820–4827 (2008).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  27. Pertl, M. M. et al. C-reactive protein predicts fatigue independently of depression in breast cancer patients before chemotherapy. Brain Behav. Immun. 34, 108–119 (2013).

    CAS  PubMed  Article  Google Scholar 

  28. Wratten, C. et al. Fatigue during breast radiotherapy and its relationship to biological factors. Int. J. Radiat. Oncol. Biol. Phys. 59, 160–167 (2004).

    PubMed  Article  Google Scholar 

  29. Fagundes, C. P. et al. Fatigue and herpesvirus latency in women newly diagnosed with breast cancer. Brain Behav. Immun. 26, 394–400 (2012).

    PubMed  Article  Google Scholar 

  30. Arpin, D. et al. Early variations of circulating interleukin-6 and interleukin-10 levels during thoracic radiotherapy are predictive for radiation pneumonitis. J. Clin. Oncol. 23, 8748–8756 (2005).

    CAS  PubMed  Article  Google Scholar 

  31. Bower, J. E. et al. Inflammation and behavioural symptoms after breast cancer treatment: do fatigue, depression, and sleep disturbance share a common underlying mechanism? J. Clin. Oncol. 29, 3517–3522 (2011).

    PubMed  PubMed Central  Article  Google Scholar 

  32. Wang, X. S. et al. Inflammatory cytokines are associated with the development of symptom burden in patients with NSCLC undergoing concurrent chemoradiation therapy. Brain Behav. Immun. 24, 968–974 (2010).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  33. Wang, X. S. et al. Serum sTNF-R1, IL-6, and the development of fatigue in patients with gastrointestinal cancer undergoing chemoradiation therapy. Brain Behav. Immun. 26, 699–705 (2012).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  34. Bower, J. E. et al. Inflammatory biomarkers and fatigue during radiation therapy for breast and prostate cancer. Clin. Cancer Res. 15, 5534–5540 (2009).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  35. Greenberg, D. B., Grey, J. L., Mannix, C. M., Eisenthal, S. & Carey, M. Treatment-related fatigue and serum interleukin-1 levels in patients during external beam irradiation for prostate cancer. J. Pain Symptom Manage. 8, 196–200 (1993).

    CAS  PubMed  Article  Google Scholar 

  36. Geinitz, H. et al. Fatigue, serum cytokine levels, and blood cell counts during radiotherapy of patients with breast cancer. Int. J. Radiat. Oncol. Biol. Phys. 51, 691–698 (2001).

    CAS  PubMed  Article  Google Scholar 

  37. Ahlberg, K., Ekman, T. & Gaston-Johansson, F. Levels of fatigue compared to levels of cytokines and haemoglobin during pelvic radiotherapy: a pilot study. Biol. Res. Nurs. 5, 203–210 (2004).

    PubMed  Article  Google Scholar 

  38. Liu, L. et al. Fatigue and sleep quality are associated with changes in inflammatory markers in breast cancer patients undergoing chemotherapy. Brain Behav. Immun. 26, 706–713 (2012).

    PubMed  PubMed Central  Article  Google Scholar 

  39. Wang, X. S. et al. Serum interleukin-6 predicts the development of multiple symptoms at nadir of allogeneic haematopoietic stem cell transplantation. Cancer 113, 2102–2109 (2008).

    PubMed  Article  Google Scholar 

  40. Bower, J. E., Ganz, P. A., Aziz, N. & Fahey, J. L. Fatigue and proinflammatory cytokine activity in breast cancer survivors. Psychosom. Med. 64, 604–611 (2002).

    PubMed  Article  Google Scholar 

  41. Collado-Hidalgo, A., Bower, J. E., Ganz, P. A., Cole, S. W. & Irwin, M. R. Inflammatory biomarkers for persistent fatigue in breast cancer survivors. Clin. Cancer Res. 12, 2759–2766 (2006).

    CAS  PubMed  Article  Google Scholar 

  42. Bower, J. E. et al. Inflammatory responses to psychological stress in fatigued breast cancer survivors: relationship to glucocorticoids. Brain Behav. Immun. 21, 251–258 (2007).

    CAS  PubMed  Article  Google Scholar 

  43. Alexander, S., Minton, O., Andrews, P. & Stone, P. A comparison of the characteristics of disease-free breast cancer survivors with or without cancer-related fatigue syndrome. Eur. J. Cancer 45, 384–392 (2009).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  44. Orre, I. J. et al. Higher levels of fatigue are associated with higher CRP levels in disease-free breast cancer survivors. J. Psychosom. Res. 71, 136–141 (2011).

    PubMed  Article  Google Scholar 

  45. Alfano, C. M. et al. Fatigue, inflammation, and ω-3 and ω-6 fatty acid intake among breast cancer survivors. J. Clin. Oncol. 30, 1280–1287 (2012).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  46. Orre, I. J. et al. Levels of circulating interleukin-1 receptor antagonist and C-reactive protein in long-term survivors of testicular cancer with chronic cancer-related fatigue. Brain Behav. Immun. 23, 868–874 (2009).

    CAS  PubMed  Article  Google Scholar 

  47. Schrepf, A. et al. Cortisol and inflammatory processes in ovarian cancer patients following primary treatment: relationships with depression, fatigue, and disability. Brain Behav. Immun. 30 (Suppl.), S126–S134 (2013).

    CAS  PubMed  Article  Google Scholar 

  48. Bower, J. E., Ganz, P. A., Irwin, M. R., Arevalo, J. M. & Cole, S. W. Fatigue and gene expression in human leucocytes: increased NF-κB and decreased glucocorticoid signalling in breast cancer survivors with persistent fatigue. Brain Behav. Immun. 25, 147–150 (2011).

    CAS  PubMed  Article  Google Scholar 

  49. Landmark-Hoyvik, H. et al. Alterations of gene expression in blood cells associated with chronic fatigue in breast cancer survivors. Pharmacogenomics J. 9, 333–340 (2009).

    CAS  PubMed  Article  Google Scholar 

  50. Light, K. C. et al. Differing leucocyte gene expression profiles associated with fatigue in patients with prostate cancer versus chronic fatigue syndrome. Psychoneuroendocrinology 38, 2983–2995 (2013).

    CAS  PubMed  Article  Google Scholar 

  51. Saligan, L. N. et al. Upregulation of α-synuclein during localized radiation therapy signals the association of cancer-related fatigue with the activation of inflammatory and neuroprotective pathways. Brain Behav. Immun. 27, 63–70 (2013).

    CAS  PubMed  Article  Google Scholar 

  52. Rotstein, S., Blomgren, H., Petrini, B., Wasserman, J. & Baral, E. Long term effects on the immune system following local radiation therapy for breast cancer. I. Cellular composition of the peripheral blood lymphocyte population. Int. J. Radiat. Oncol. Biol. Phys. 11, 921–925 (1985).

    CAS  PubMed  Article  Google Scholar 

  53. Solomayer, E. F. et al. Influence of adjuvant hormone therapy and chemotherapy on the immune system analysed in the bone marrow of patients with breast cancer. Clin. Cancer Res. 9, 174–180 (2003).

    CAS  PubMed  Google Scholar 

  54. Bower, J. E., Ganz, P. A., Aziz, N., Fahey, J. L. & Cole, S. W. T-cell homeostasis in breast cancer survivors with persistent fatigue. J. Natl Cancer Inst. 95, 1165–1168 (2003).

    PubMed  Article  Google Scholar 

  55. Minton, O. & Stone, P. C. A comparison of cognitive function, sleep and activity levels in disease-free breast cancer patients with or without cancer-related fatigue syndrome. BMJ Support Palliat. Care 2, 231–238 (2013).

    Article  Google Scholar 

  56. Reinertsen, K. et al. Predictors and course of chronic fatigue in long-term breast cancer survivors. J. Cancer Surviv. 4, 405–414 (2010).

    PubMed  PubMed Central  Article  Google Scholar 

  57. Fagundes, C. P., Lindgren, M. E., Shapiro, C. L. & Kiecolt-Glaser, J. K. Child maltreatment and breast cancer survivors: social support makes a difference for quality of life, fatigue and cancer stress. Eur. J. Cancer 48, 728–736 (2012).

    PubMed  PubMed Central  Article  Google Scholar 

  58. Bower, J. E. Cancer-related fatigue: links with inflammation in cancer patients and survivors. Brain Behav. Immun. 21, 863–871 (2007).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  59. Irwin, M. R. & Cole, S. W. Reciprocal regulation of the neural and innate immune systems. Nat. Rev. Immunol. 11, 625–632 (2011).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  60. Raison, C. L. & Miller, A. H. When not enough is too much: the role of insufficient glucocorticoid signalling in the pathophysiology of stress-related disorders. Am. J. Psychiatry 160, 1554–1565 (2003).

    Article  PubMed  Google Scholar 

  61. Bower, J. E., Ganz, P. A. & Aziz, N. Altered cortisol response to psychologic stress in breast cancer survivors with persistent fatigue. Psychosom. Med. 67, 277–280 (2005).

    PubMed  Article  Google Scholar 

  62. Bower, J. E. et al. Diurnal cortisol rhythm and fatigue in breast cancer survivors. Psychoneuroendocrinology 30, 92–100 (2005).

    CAS  PubMed  Article  Google Scholar 

  63. Weinrib, A. Z. et al. Diurnal cortisol dysregulation, functional disability, and depression in women with ovarian cancer. Cancer 116, 4410–4419 (2010).

    PubMed  Article  Google Scholar 

  64. Cole, S. W. et al. Social regulation of gene expression in human leucocytes. Genome Biol. 8, R189 (2007).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  65. Miller, G. E. et al. A functional genomic fingerprint of chronic stress in humans: blunted glucocorticoid and increased NF-κB signalling. Biol. Psychiatry 64, 266–272 (2008).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  66. Fagundes, C. P. et al. Sympathetic and parasympathetic activity in cancer-related fatigue: more evidence for a physiological substrate in cancer survivors. Psychoneuroendocrinology 36, 1137–1147 (2011).

    PubMed  PubMed Central  Article  Google Scholar 

  67. Crosswell, A. D., Lockwood, K. G., Ganz, P. A. & Bower, J. E. Low heart rate variability and cancer-related fatigue in breast cancer survivors. Psychoneuroendocrinology 45, 58–66 (2014).

    PubMed  PubMed Central  Article  Google Scholar 

  68. Dimeo, F. et al. Physical performance, depression, immune status and fatigue in patients with haematological malignancies after treatment. Ann. Oncol. 15, 1237–1242 (2004).

    CAS  PubMed  Article  Google Scholar 

  69. de Raaf, P. J. et al. Inflammation and fatigue dimensions in advanced cancer patients and cancer survivors: an explorative study. Cancer 118, 6005–6011 (2012).

    PubMed  Article  Google Scholar 

  70. van Zuiden, M. et al. Glucocorticoid sensitivity of leucocytes predicts PTSD, depressive and fatigue symptoms after military deployment: A prospective study. Psychoneuroendocrinology 37, 1822–1836 (2012).

    CAS  PubMed  Article  Google Scholar 

  71. Dhruva, A. et al. Trajectories of fatigue in patients with breast cancer before, during, and after radiation therapy. Cancer Nurs. 33, 201–212 (2010).

    PubMed  PubMed Central  Article  Google Scholar 

  72. Aouizerat, B. E. et al. Preliminary evidence of a genetic association between tumour necrosis factor alpha and the severity of sleep disturbance and morning fatigue. Biol. Res. Nurs. 11, 27–41 (2009).

    CAS  PubMed  Article  Google Scholar 

  73. Miaskowski, C. et al. Preliminary evidence of an association between a functional interleukin-6 polymorphism and fatigue and sleep disturbance in oncology patients and their family caregivers. J. Pain Symptom Manage. 40, 531–544 (2010).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  74. Jim, H. S. et al. Genetic predictors of fatigue in prostate cancer patients treated with androgen deprivation therapy: Preliminary findings. Brain Behav. Immun. 26, 1030–1036 (2012).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  75. Reyes-Gibby, C. C. et al. Genetic variations in interleukin-8 and interleukin-10 are associated with pain, depressed mood, and fatigue in lung cancer patients. J. Pain Symptom Manage. 46, 161–172 (2013).

    PubMed  Article  CAS  Google Scholar 

  76. Rausch, S. M. et al. Relationship between cytokine gene single nucleotide polymorphisms and symptom burden and quality of life in lung cancer survivors. Cancer 116, 4103–4113 (2010).

    CAS  PubMed  Article  Google Scholar 

  77. Collado-Hidalgo, A., Bower, J. E., Ganz, P. A., Irwin, M. R. & Cole, S. W. Cytokine gene polymorphisms and fatigue in breast cancer survivors: Early findings. Brain. Behav. Immun. 22, 1197–1200 (2008).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  78. Bower, J. E. et al. Cytokine genetic variations and fatigue among patients with breast cancer. J. Clin. Oncol. 31, 1656–1661 (2013).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  79. Reinertsen, K. V. et al. Fatigued breast cancer survivors and gene polymorphisms in the inflammatory pathway. Brain. Behav. Immun. 25, 1376–1383 (2011).

    CAS  PubMed  Article  Google Scholar 

  80. Carlo-Stella, N. et al. A first study of cytokine genomic polymorphisms in CFS: positive association of TNF-857 and IFNgamma 874 rare alleles. Clin. Exp. Rheumatol. 24, 179–182 (2006).

    CAS  PubMed  Google Scholar 

  81. Piraino, B., Vollmer-Conna, U. & Lloyd, A. R. Genetic associations of fatigue and other symptom domains of the acute sickness response to infection. Brain Behav. Immun. 26, 552–558 (2012).

    CAS  PubMed  Article  Google Scholar 

  82. Goldstein, D. et al. Cancer-related fatigue in women with breast cancer: outcomes of a 5-year prospective cohort study. J. Clin. Oncol. 30, 1805–1812 (2012).

    PubMed  Article  Google Scholar 

  83. Stone, P., Richards, M., A'Hern, R. & Hardy, J. Fatigue in patients with cancers of the breast or prostate undergoing radical radiotherapy. J. Pain Symptom Manage. 22, 1007–1015 (2001).

    CAS  PubMed  Article  Google Scholar 

  84. Goedendorp, M. M., Gielissen, M. F., Verhagen, C. A. & Bleijenberg, G. Development of fatigue in cancer survivors: a prospective follow-up study from diagnosis into the year after treatment. J. Pain Symptom Manage. 45, 213–222 (2013).

    PubMed  Article  Google Scholar 

  85. Geinitz, H. et al. Fatigue in patients with adjuvant radiation therapy for breast cancer: long-term follow-up. J. Cancer Res. Clin. Oncol. 130, 327–333 (2004).

    PubMed  Article  Google Scholar 

  86. Jacobsen, P. B., Donovan, K. A. & Weitzner, M. A. Distinguishing fatigue and depression in patients with cancer. Semin. Clin. Neuropsychiatry 8, 229–240 (2003).

    PubMed  Google Scholar 

  87. Miaskowski, C. et al. Trajectories of fatigue in men with prostate cancer before, during, and after radiation therapy. J. Pain Symptom Manage. 35, 632–643 (2008).

    PubMed  PubMed Central  Article  Google Scholar 

  88. Andrykowski, M. A., Schmidt, J. E., Salsman, J. M., Beacham, A. O. & Jacobsen, P. B. Use of a case definition approach to identify cancer-related fatigue in women undergoing adjuvant therapy for breast cancer. J. Clin. Oncol. 23, 6613–6622 (2005).

    PubMed  Article  Google Scholar 

  89. Andrykowski, M. A., Donovan, K. A., Laronga, C. & Jacobsen, P. B. Prevalence, predictors, and characteristics of off-treatment fatigue in breast cancer survivors. Cancer 116, 5740–5748 (2010).

    PubMed  Article  Google Scholar 

  90. Bower, J. E., Crosswell, A. D. & Slavich, G. M. Childhood adversity and cumulative life stress: risk factors for cancer-related fatigue. Clin. Psychol. Sci. http://dox.doi.org/10.1177/2167702613496243.

  91. Ancoli-Israel, S., Moore, P. J. & Jones, V. The relationship between fatigue and sleep in cancer patients: a review. Eur. J. Cancer Care (Engl.) 10, 245–255 (2001).

    CAS  Article  Google Scholar 

  92. Jim, H. S. et al. Lagged relationships among sleep disturbance, fatigue, and depressed mood during chemotherapy. Health Psychol. 32, 768–774 (2013).

    PubMed  PubMed Central  Article  Google Scholar 

  93. Berger, A. M. Patterns of fatigue and activity and rest during adjuvant breast cancer chemotherapy. Oncol. Nurs. Forum 25, 51–62 (1998).

    CAS  PubMed  Google Scholar 

  94. Winters-Stone, K. M., Bennett, J. A., Nail, L. & Schwartz, A. Strength, physical activity, and age predict fatigue in older breast cancer survivors. Oncol. Nurs. Forum 35, 815–821 (2008).

    PubMed  Article  Google Scholar 

  95. Neil, S. E., Klika, R. J., Garland, S. J., McKenzie, D. C. & Campbell, K. L. Cardiorespiratory and neuromuscular deconditioning in fatigued and non-fatigued breast cancer survivors. Support. Care Cancer 21, 873–881 (2013).

    PubMed  Article  Google Scholar 

  96. Alfano, C. M. et al. Physical activity, long-term symptoms, and physical health-related quality of life among breast cancer survivors: a prospective analysis. J. Cancer Surviv. 1, 116–128 (2007).

    PubMed  PubMed Central  Article  Google Scholar 

  97. Jacobsen, P. B., Andrykowski, M. A. & Thors, C. L. Relationship of catastrophizing to fatigue among women receiving treatment for breast cancer. J. Consult. Clin. Psychol. 72, 355–361 (2004).

    PubMed  PubMed Central  Article  Google Scholar 

  98. Montgomery, G. H., Schnur, J. B., Erblich, J., Diefenbach, M. A. & Bovbjerg, D. H. Presurgery psychological factors predict pain, nausea, and fatigue one week after breast cancer surgery. J. Pain Symptom Manage. 39, 1043–1052 (2010).

    PubMed  PubMed Central  Article  Google Scholar 

  99. Cramp, F. & Byron-Daniel, J. Exercise for the management of cancer-related fatigue in adults. Cochrane Database of Systematic Review Issue 11. Art. No.: CD006145. http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD006145.pub3/abstract.

  100. Brown, J. C. et al. Efficacy of exercise interventions in modulating cancer-related fatigue among adult cancer survivors: a meta-analysis. Cancer Epidemiol. Biomarkers Prev. 20, 123–133 (2011).

    PubMed  Article  Google Scholar 

  101. Puetz, T. W. & Herring, M. P. Differential effects of exercise on cancer-related fatigue during and following treatment: a meta-analysis. Am. J. Prev. Med. 43, e1–e24 (2012).

    PubMed  Article  Google Scholar 

  102. Pinto, B. M., Frierson, G. M., Rabin, C., Trunzo, J. J. & Marcus, B. H. Home-based physical activity intervention for breast cancer patients. J. Clin. Oncol. 23, 3577–3587 (2005).

    PubMed  Article  Google Scholar 

  103. Courneya, K. S. et al. Randomized controlled trial of the effects of aerobic exercise on physical functioning and quality of life in lymphoma patients. J. Clin. Oncol. 27, 4605–4612 (2009).

    PubMed  Article  Google Scholar 

  104. Strasser, B., Steindorf, K., Wiskemann, J. & Ulrich, C. M. Impact of resistance training in cancer survivors: a meta-analysis. Med. Sci. Sports Exerc. 45, 2080–2090 (2013).

    PubMed  Article  Google Scholar 

  105. Schmitz, K. H. et al. American College of Sports Medicine roundtable on exercise guidelines for cancer survivors. Med. Sci. Sports Exerc. 42, 1409–1426 (2010).

    PubMed  Article  Google Scholar 

  106. Courneya, K. S. et al. Three independent factors predicted adherence in a randomized controlled trial of resistance exercise training among prostate cancer survivors. J. Clin. Epidemiol. 57, 571–579 (2004).

    PubMed  Article  Google Scholar 

  107. Jacobsen, P. B., Donovan, K. A., Vadaparampil, S. T. & Small, B. J. Systematic review and meta-analysis of psychological and activity-based interventions for cancer-related fatigue. Health Psychol. 26, 660–667 (2007).

    PubMed  PubMed Central  Article  Google Scholar 

  108. Kangas, M., Bovbjerg, D. H. & Montgomery, G. H. Cancer-related fatigue: a systematic and meta-analytic review of non-pharmacological therapies for cancer patients. Psychol. Bull. 134, 700–741 (2008).

    PubMed  Article  Google Scholar 

  109. Goedendorp, M. M., Gielissen, M. F., Verhagen, C. A. & Bleijenberg, G. Psychosocial interventions for reducing fatigue during cancer treatment in adults. Cochrane Database of Systematic Review Issue 1. Art. No.: CD006953. http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD006953.pub2/abstract.

  110. Yates, P. et al. Randomized controlled trial of an educational intervention for managing fatigue in women receiving adjuvant chemotherapy for early-stage breast cancer. J. Clin. Oncol. 23, 6027–6036 (2005).

    PubMed  Article  Google Scholar 

  111. Armes, J., Chalder, T., Addington-Hall, J., Richardson, A. & Hotopf, M. A randomized controlled trial to evaluate the effectiveness of a brief, behaviourally oriented intervention for cancer-related fatigue. Cancer 110, 1385–1395 (2007).

    PubMed  Article  Google Scholar 

  112. Montgomery, G. H. et al. Fatigue during breast cancer radiotherapy: an initial randomized study of cognitive-behavioural therapy plus hypnosis. Health Psychol. 28, 317–322 (2009).

    PubMed  Article  Google Scholar 

  113. Stanton, A. L. et al. Outcomes from the moving beyond cancer psychoeducational, randomized, controlled trial with breast cancer patients. J. Clin. Oncol. 23, 6009–6018 (2005).

    PubMed  Article  Google Scholar 

  114. Fillion, L. et al. A brief intervention for fatigue management in breast cancer survivors. Cancer Nurs. 31, 145–159 (2008).

    PubMed  Article  Google Scholar 

  115. Gielissen, M. F., Verhagen, S., Witjes, F. & Bleijenberg, G. Effects of cognitive behaviour therapy in severely fatigued disease-free cancer patients compared with patients waiting for cognitive behaviour therapy: a randomized controlled trial. J. Clin. Oncol. 24, 4882–4887 (2006).

    PubMed  Article  Google Scholar 

  116. Gielissen, M. F., Verhagen, C. A. & Bleijenberg, G. Cognitive behaviour therapy for fatigued cancer survivors: long-term follow-up. Br. J. Cancer 97, 612–618 (2007).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  117. Yun, Y. H. et al. Web-based tailored education programme for disease-free cancer survivors with cancer-related fatigue: a randomized controlled trial. J. Clin. Oncol. 30, 1296–1303 (2012).

    PubMed  Article  Google Scholar 

  118. Molassiotis, A. et al. Acupuncture for cancer-related fatigue in patients with breast cancer: a pragmatic randomized controlled trial. J. Clin. Oncol. 30, 4470–4476 (2012).

    PubMed  Article  Google Scholar 

  119. Molassiotis, A., Sylt, P. & Diggins, H. The management of cancer-related fatigue after chemotherapy with acupuncture and acupressure: a randomised controlled trial. Complement. Ther. Med. 15, 228–237 (2007).

    PubMed  Article  Google Scholar 

  120. Deng, G. et al. Acupuncture for the treatment of post-chemotherapy chronic fatigue: a randomized, blinded, sham-controlled trial. Support. Care Cancer 21, 1735–1741 (2013).

    PubMed  PubMed Central  Article  Google Scholar 

  121. van der Lee, M. L. & Garssen, B. Mindfulness-based cognitive therapy reduces chronic cancer-related fatigue: a treatment study. Psychooncology 21, 264–272 (2012).

    PubMed  Article  Google Scholar 

  122. Bower, J. E. et al. Yoga for persistent fatigue in breast cancer survivors: a randomized controlled trial. Cancer 118, 3766–3775 (2012).

    PubMed  Article  Google Scholar 

  123. Jain, S. et al. Complementary medicine for fatigue and cortisol variability in breast cancer survivors: a randomized controlled trial. Cancer 118, 777–787. (2011).

    PubMed  Article  CAS  Google Scholar 

  124. Chandwani, K. D. et al. Yoga improves quality of life and benefit finding in women undergoing radiotherapy for breast cancer. J. Soc. Integr. Oncol. 8, 43–55 (2010).

    PubMed  Google Scholar 

  125. Minton, O., Richardson, A., Sharpe, M., Hotopf, M. & Stone, P. A systematic review and meta-analysis of the pharmacological treatment of cancer-related fatigue. J. Natl Cancer Inst. 100, 1155–1166 (2008).

    CAS  PubMed  Article  Google Scholar 

  126. Stockler, M. R. et al. Effect of sertraline on symptoms and survival in patients with advanced cancer, but without major depression: a placebo-controlled double-blind randomised trial. Lancet Oncol. 8, 603–612 (2007).

    CAS  PubMed  Article  Google Scholar 

  127. Yennurajalingam, S. et al. Reduction of cancer-related fatigue with dexamethasone: a double-blind, randomized, placebo-controlled trial in patients with advanced cancer. J. Clin. Oncol. 31, 3076–3082 (2013).

    CAS  PubMed  Article  Google Scholar 

  128. Minton, O., Richardson, A., Sharpe, M., Hotopf, M. & Stone, P. C. Psychostimulants for the management of cancer-related fatigue: a systematic review and meta-analysis. J. Pain Symptom Manage. 41, 761–767 (2011).

    CAS  PubMed  Article  Google Scholar 

  129. Lower, E. E. et al. Efficacy of dexmethylphenidate for the treatment of fatigue after cancer chemotherapy: a randomized clinical trial. J. Pain Symptom Manage. 38, 650–662 (2009).

    CAS  PubMed  Article  Google Scholar 

  130. Bruera, E. et al. Methylphenidate and/or a nursing telephone intervention for fatigue in patients with advanced cancer: a randomized, placebo-controlled, phase II trial. J. Clin. Oncol. 31, 2421–2427 (2013).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  131. Moraska, A. R. et al. Phase III, randomized, double-blind, placebo-controlled study of long-acting methylphenidate for cancer-related fatigue: North Central Cancer Treatment Group NCCTG-N05C7 trial. J. Clin. Oncol. 28, 3673–3679 (2010).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  132. Jean-Pierre, P. et al. A phase 3 randomized, placebo-controlled, double-blind, clinical trial of the effect of modafinil on cancer-related fatigue among 631 patients receiving chemotherapy: a University of Rochester Cancer Centre Community Clinical Oncology Program Research base study. Cancer 116, 3513–3520 (2010).

    CAS  PubMed  Article  Google Scholar 

  133. Monk, J. P. et al. Assessment of tumour necrosis factor alpha blockade as an intervention to improve tolerability of dose-intensive chemotherapy in cancer patients. J. Clin. Oncol. 24, 1852–1859 (2006).

    CAS  PubMed  Article  Google Scholar 

  134. Tookman, A. J., Jones, C. L., DeWitte, M. & Lodge, P. J. Fatigue in patients with advanced cancer: a pilot study of an intervention with infliximab. Support. Care Cancer 16, 1131–1140 (2008).

    CAS  PubMed  Article  Google Scholar 

  135. Tyring, S. et al. Etanercept and clinical outcomes, fatigue, and depression in psoriasis: double-blind placebo-controlled randomised phase III trial. Lancet 367, 29–35 (2006).

    CAS  Article  PubMed  Google Scholar 

  136. Raison, C. L. et al. A randomized controlled trial of the tumour necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers. JAMA Psychiatry 70, 31–41 (2013).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  137. Cruciani, R. A. et al. L-carnitine supplementation for the management of fatigue in patients with cancer: an Eastern Cooperative Oncology Group phase III, randomized, double-blind, placebo-controlled trial. J. Clin. Oncol. 30, 3864–3869 (2012).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  138. Barton, D. L. et al. Wisconsin Ginseng (Panax quinquefolius) to improve cancer-related fatigue: a randomized, double-blind trial, N07C2. J. Natl Cancer Inst. 105, 1230–1238 (2013).

    PubMed  PubMed Central  Article  Google Scholar 

  139. Bower, J. E. et al. Screening, assessment and management of fatigue in adult survivors of cancer: an American Society of Clinical Oncology Clinical Practice Guideline Adaptation J. Clin. Oncol. 32, 1840–1850 (2014).

    PubMed  PubMed Central  Article  Google Scholar 

  140. Plaisance, E. P. & Grandjean, P. W. Physical activity and high-sensitivity C-reactive protein. Sports Med. 36, 443–458 (2006).

    PubMed  Article  Google Scholar 

  141. Bower, J. E. et al. Yoga reduces inflammatory signalling in fatigued breast cancer survivors: A randomized controlled trial. Psychoneuroendocrinology 43, 20–29 (2014).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  142. Bower, J. E. et al. Effects of mindfulness meditation on stress and inflammation in breast cancer survivors: a randomized controlled trial (American Psychosomatic Society, San Francisco, CA, 2014).

  143. Antoni, M. H. et al. Cognitive-behavioural stress management reverses anxiety-related leucocyte transcriptional dynamics. Biol. Psychiatry 71, 366–372 (2012).

    CAS  PubMed  Article  Google Scholar 

  144. Minton, O. & Stone, P. A systematic review of the scales used for the measurement of cancer-related fatigue (CRF). Ann. Oncol. 20, 17–25 (2009).

    CAS  PubMed  Article  Google Scholar 

  145. Mendoza, T. R. et al. The rapid assessment of fatigue severity in cancer patients: use of the Brief Fatigue Inventory. Cancer 85, 1186–1196 (1999).

    CAS  PubMed  Article  Google Scholar 

  146. Cella, D., Peterman, A., Passik, S., Jacobsen, P. & Breitbart, W. Progress toward guidelines for the management of fatigue. Oncology 12, 369–377 (1998).

    CAS  PubMed  Google Scholar 

  147. Donovan, K. A., McGinty, H. L. & Jacobsen, P. B. A systematic review of research using the diagnostic criteria for cancer-related fatigue. Psychooncology 22, 737–744 (2013).

    PubMed  Article  Google Scholar 

  148. Miller, A. H., Haroon, E., Raison, C. L. & Felger, J. C. Cytokine targets in the brain: impact on neurotransmitters and neurocircuits. Depress. Anxiety 30, 297–306 (2013).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  149. Kirkwood, J. Cancer immunotherapy: the interferon-alpha experience. Semin. Oncol. 29, 18–26 (2002).

    CAS  PubMed  Article  Google Scholar 

  150. Reichenberg, A. et al. Cytokine-associated emotional and cognitive disturbances in humans. Arch. Gen. Psychiatry 58, 445–452 (2001).

    CAS  PubMed  Article  Google Scholar 

  151. Cho, H. J., Kivimaki, M., Bower, J. E. & Irwin, M. R. Association of C-reactive protein and interleukin-6 with new-onset fatigue in the Whitehall II prospective cohort study. Psychol. Med. 43, 1773–1783 (2013).

    CAS  PubMed  Article  Google Scholar 

  152. Cho, H. J., Seeman, T. E., Bower, J. E., Kiefe, C. I. & Irwin, M. R. Prospective association between C-reactive protein and fatigue in the coronary artery risk development in young adults study. Biol. Psychiatry 66, 871–878 (2009).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

Download references

Acknowledgements

The author acknowledges research support from the NIH/National Cancer Institute (grant 5R01CA160427).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Julienne E. Bower.

Ethics declarations

Competing interests

The author declares no competing financial interests.

PowerPoint slides

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Bower, J. Cancer-related fatigue—mechanisms, risk factors, and treatments. Nat Rev Clin Oncol 11, 597–609 (2014). https://doi.org/10.1038/nrclinonc.2014.127

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrclinonc.2014.127

Further reading

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing