Quality of Life Research

, Volume 22, Issue 9, pp 2279–2292

Deriving clinically meaningful cut-scores for fatigue in a cohort of breast cancer survivors: a Health, Eating, Activity, and Lifestyle (HEAL) Study

  • Angela M. Stover
  • Bryce B. Reeve
  • Barbara F. Piper
  • Catherine M. Alfano
  • Ashley Wilder Smith
  • Sandra A. Mitchell
  • Leslie Bernstein
  • Kathy B. Baumgartner
  • Anne McTiernan
  • Rachel Ballard-Barbash



To empirically determine clinically meaningful cut-scores on the 0–10 response scale of the revised Piper Fatigue Scale (PFS-R) and its shorter version (PFS-12). Breast cancer survivors were classified (i.e., none, mild, moderate, or severe fatigue) based on the cut-scores, and relationships between these cut-scores and decrements in health-related quality of life (HRQOL) were examined.


A total of 857 breast cancer survivors, stages in situ-IIIa, from the Health, Eating, Activity, and Lifestyle (HEAL) Study were eligible. Survivors completed the PFS-R, SF-36, and a sexual health scale approximately 3 years after diagnosis. Multivariate analysis of covariance was used to examine five fatigue severity cut-score models, controlling for demographics, clinical characteristics, comorbidity, and antidepressant use. Multivariate regression was used to examine HRQOL decrements by cut-score category.


Analyses supported two similar fatigue severity cut-score models for the PFS-R and PFS-12: ModelA.) none (0), mild (1–3), moderate (4–6), and severe (7–10); and ModelD.) none (0), mild (1–2), moderate (3–5), and severe (6–10). For every threshold increase in fatigue severity, clinically meaningful decrements in physical, mental, and sexual health scores were observed, supporting construct validity of the fatigue cut-scores.


Standardized fatigue cut-scores may enhance interpretability and comparability across studies and populations and guide treating planning.


Cancer-related fatigue Breast cancer survivors Measurement Piper Fatigue Scale Health-related quality of life 



Body mass index


Cancer inventory for problem situations


Cancer-related fatigue


Health, Eating, Activity, and Lifestyle Study


Health-related quality of life


Multivariate analysis of covariance


Mental Component Score for the SF-36


Physical Component Score for the SF-36


Piper Fatigue Scale-Revised


Piper Fatigue Scale-12


Surveillance, epidemiology, and end results (cancer registries)


Medical Outcomes Study Short Form-36


  1. 1.
    Meeske, K., Smith, A. W., Alfano, C. M., McGregor, B. A., McTiernan, A., Baumgartner, K. B., et al. (2007). Fatigue in breast cancer survivors two to five years post diagnosis: A HEAL Study report. Quality of Life Research, 16, 947–960.PubMedCrossRefGoogle Scholar
  2. 2.
    Kim, J.-E., Dodd, M. J., Aouizerat, B. E., Jahan, T., & Miaskowski, C. (2009). A review of the prevalence and impact of multiple symptoms in oncology patients. Journal of Pain and Symptom Management, 37, 715–736.CrossRefGoogle Scholar
  3. 3.
    Scott, J. A., Lasch, K., Barsevick, A., & Piault-Louis, E. (2011). Patient-reported outcomes of fatigue consortium (PROOF-C). Patients’ experiences with cancer-related fatigue: A systematic review and synthesis of qualitative research. Oncology Nursing Forum, 38, E191–E203.PubMedCrossRefGoogle Scholar
  4. 4.
    Ganz, P. A., Desmond, K. A., Leedham, B., Rowland, J. H., Meyerowitz, B. E., & Belin, T. R. (2002). Quality of life in long-term, disease-free survivors of breast cancer: A follow-up study. Journal of the National Cancer Institute, 94, 39–49.PubMedCrossRefGoogle Scholar
  5. 5.
    Mitchell, S. (2010). Cancer-related fatigue: State of the science. Physical Medicine and Rehabilitation, 2, 364–383.Google Scholar
  6. 6.
    Piper, B. F., & Cella, D. (2010). Cancer-related fatigue: definitions and clinical subtypes. Journal of the National Comprehensive Cancer Network, 8, 958–966.PubMedGoogle Scholar
  7. 7.
    Knowles, G., Borthwick, D., McNamara, S., Miller, M., & Leggot, L. (2000). Survey of nurses’ assessment of cancer-related fatigue. European Journal of Cancer Care, 9, 105–113.PubMedCrossRefGoogle Scholar
  8. 8.
    Pachman, D. R., Barton, D. L., Swetz, K. M., & Loprinzi, C. L. (2012). Troublesome symptoms in cancer survivors: fatigue, insomnia, neuropathy, and pain. Journal of Clinical Oncology, 30, 3687–3696.PubMedCrossRefGoogle Scholar
  9. 9.
    Barsevick, A. M., & Cleeland, C. S. (2010). ASCPRO recommendations for the assessment of fatigue as an outcome in clinical trials. Journal of Pain and Symptom Management, 39, 1086–1099.PubMedCrossRefGoogle Scholar
  10. 10.
    The Cancer-Related Fatigue Guidelines (Version 4.2007) in The Complete Library of NCCN Clinical Practice Guidelines in Oncology [CD-ROM] Jenkintown, Pennsylvania: © 2006 National Comprehensive Cancer Network, Inc.; Mar, 2008. To view the most recent and complete version of the guideline, go to www.nccn.org.
  11. 11.
    Berger, A. M., Abernethy, A. P., & Atkinson, A. (2010). Cancer-related fatigue. JNCCN, 8, 904–931.PubMedGoogle Scholar
  12. 12.
    Mitchell, S. A., Beck, S. L., & Eaton, L. H. (2009). ONS putting evidence into practice (PEP): fatigue. In L. H. Eaton & J. M. Tipton (Eds.), Putting evidence into practice. Pittsburgh: Oncology Nursing Society.Google Scholar
  13. 13.
    Cella, D., Davis, K., Breitbart, W., Curt, G., for the Fatigue Coalition. (2001). Cancer-related fatigue: Prevalence of proposed diagnostic criteria in a United States sample of cancer survivors. Journal of Clinical Oncology, 19, 3385–3391.Google Scholar
  14. 14.
    Cella, D., Peterman, A., Passik, S., et al. (1998). Progress towards guidelines for the management of fatigue. Oncology, 12, 369–377.PubMedGoogle Scholar
  15. 15.
    Vogelzang, N., Breitbart, W., Cella, D., et al. (1997). Patient, caregiver, and oncologist perceptions of cancer-related fatigue: Results of a tri-part assessment survey. Seminars in Hematology, 34(Supplement 2), 4–12.PubMedGoogle Scholar
  16. 16.
    Agasi-Idenburg, C., Velthuis, M., & Wittink, H. (2010). Quality criteria and user-friendliness in self-reported questionnaires on cancer-related fatigue: A review. Journal of Clinical Epidemiology, 63, 705–711.PubMedCrossRefGoogle Scholar
  17. 17.
    Dittner, A. J., Wessely, S. C., & Brown, R. G. (2004). The assessment of fatigue: A practical guide for clinicians and researchers. Journal of Psychosomatic Research, 56, 157–170.PubMedCrossRefGoogle Scholar
  18. 18.
    Jean-Pierre, P., & Figueroa-Moseley, C. D. (2007). Assessment of cancer-related fatigue: Implications for clinical diagnosis and treatment. Oncologist, 12(Supplement 1), 11–21.PubMedCrossRefGoogle Scholar
  19. 19.
    Minton, O., & Stone, P. (2009). A systematic review of the scales used for the measurement of cancer-related fatigue (CRF). Annals of Oncology, 20, 17–25.PubMedCrossRefGoogle Scholar
  20. 20.
    Mota, D. D., & Pimenta, C. A. (2006). Self-report instruments for fatigue assessment: A systematic review. Research and Theory for Nursing Practice, 20, 49–78.PubMedCrossRefGoogle Scholar
  21. 21.
    Whitehead, L. (2009). The measurement of fatigue in chronic illness: A systematic review of unidimensional and multidimensional fatigue measures. Journal of Pain and Symptom Management, 37, 107–128.PubMedCrossRefGoogle Scholar
  22. 22.
    Mendoza, T., Wang, X. S., Cleeland, C. S., Morrissey, M., Johnson, B. A., Wendt, J. K., et al. (1999). The rapid assessment of fatigue severity in cancer patients: Use of the brief fatigue inventory. Cancer, 85, 1186–1196.PubMedCrossRefGoogle Scholar
  23. 23.
    Borneman, T., Koczywas, M., Sun, V. C., Piper, B. F., Uman, G., & Ferrell, B. (2010). Reducing patient barriers to pain and fatigue management. Journal of Pain and Symptom Management, 39, 486–501.PubMedCrossRefGoogle Scholar
  24. 24.
    Weilgus, K., Berger, A. M., & Hertzog, M. (2009). Predictors of fatigue 30 days after completing anthracycline plus taxane adjuvant chemotherapy for breast cancer. Oncology Nursing Forum, 36, 38–48.CrossRefGoogle Scholar
  25. 25.
    Cullum, J. L., Wojciechowski, A. E., & Simpson, J. S. A. (2004). Bupropion sustained release treatment reduces fatigue in cancer patients. Canadian Journal of Psychiatry, 49, 139–144.Google Scholar
  26. 26.
    Cooper, M. R., Bird, H. M., & Steinberg, M. (2009). Efficacy and safety of modafinil in the treatment of cancer-related fatigue. The Annals of Pharmacotherapy, 43, 721–725.PubMedCrossRefGoogle Scholar
  27. 27.
    Jean-Pierre, P., Morrow, G. R., Roscoe, J. A., Heckler, C., Mohile, S., Janelsins, M., et al. (2010). A phase 3 randomized, placebo-controlled, doubleblind, clinical trial of the effect of modafinil on cancer-related fatigue among 631 patients receiving chemotherapy: A University of Rochester cancer center community clinical oncology program research base study. Cancer, 116, 3513–3520.PubMedCrossRefGoogle Scholar
  28. 28.
    Moss, E. L., Simpson, J. S., Pelletier, G., et al. (2006). An open-label study of the effects of bupropion SR on fatigue, depression and quality of life of mixed-site cancer patients and their partners. Psycho-oncology, 15, 259–267.PubMedCrossRefGoogle Scholar
  29. 29.
    Nering, M. L., & Ostini, R. (Eds.). (2010). Handbook of polytomous item response theory models. New York, NY: Routledge.Google Scholar
  30. 30.
    Chamberlain Wilmoth, M., Coleman, E. A., Smith, S. C., & Davis, C. (2004). Fatigue, weight gain, and altered sexuality in patients with breast cancer: Exploration of a symptom cluster. Oncology Nursing Forum, 31, 1069–1075.CrossRefGoogle Scholar
  31. 31.
    Webber, K., Mok, K., Bennett, B., Lloyd, A. R., Friedlander, M., Juraskova, I., et al. (2011). If I am in the mood, I enjoy it: An exploration of cancer-related fatigue and sexual functioning in women with breast cancer. The Oncologist, 16, 1333–1344.PubMedCrossRefGoogle Scholar
  32. 32.
    Ganz, P. A., Rowland, J. H., Desmond, K., Meyerowitz, B. E., & Wyatt, G. E. (1998). Life after breast cancer: understanding women’s health-related quality of life and sexual functioning. Journal of Clinical Oncology, 16, 501–514.PubMedGoogle Scholar
  33. 33.
    Ganz, P. A., Desmond, K. A., Belin, T. R., Meyerowitz, B. E., & Rowland, J. H. (1999). Predictors of sexual health in women after a breast cancer diagnosis. Journal of Clinical Oncology, 17, 2371–2380.PubMedGoogle Scholar
  34. 34.
    Fobair, P., & Spiegel, D. (2010). Concerns about sexuality after breast cancer. In V. T. Devita, T. S. Lawrence, & S. A. Rosenberg (Eds.), Cancer principles and practice of oncology: Annual advances in oncology (pp. 7–14). Philadelphia, PA: Lippincott Williams & Wilkins.Google Scholar
  35. 35.
    Lindau, S. T., Schumm, L. P., Laumann, E. O., Levinson, W., O’Muircheartaigh, C. A., & Waite, L. J. (2007). A study of sexuality and health among older adults in the United States. New England Journal of Medicine, 357, 762–774.PubMedCrossRefGoogle Scholar
  36. 36.
    Rubin, P. (2001). Clinical oncology: A multidisciplinary approach for physicians and students (8th ed.). Philadelphia: W. B. Saunders Company.Google Scholar
  37. 37.
    Piper, B. F., Dibble, S. L., Dodd, M. J., Weiss, M. C., Slaughter, R. E., & Paul, S. M. (1998). The revised piper fatigue scale: Psychometric evaluation in women with breast cancer. Oncology Nursing Forum, 25, 677–684.PubMedGoogle Scholar
  38. 38.
    Reeve, B. B., Stover, A. M., Alfano, C. M., Piper, B. F., Bernstein, L., Baumgartner, K., et al. (2012). Psychometric evaluation and reduction of the piper fatigue scale based on a cohort of breast cancer survivors. Breast Cancer Research and Treatment, 136, 9–20.PubMedCrossRefGoogle Scholar
  39. 39.
    McTiernan, A., Rajan, K. B., Tworoger, S. S., Irwin, M., Bernstein, L., Baumgartner, R., et al. (2003). Adiposity and sex hormones in postmenopausal breast cancer survivors. Journal of Clinical Oncology, 21, 1961–1966.PubMedCrossRefGoogle Scholar
  40. 40.
    Groenvold, M., Aagard Petersen, M., Idler, E., Bjorner, J. B., Fayers, P. M., & Mouridsen, H. T. (2007). Psychological distress and fatigue predicted recurrence and survival in primary breast cancer patients. Breast Cancer Research and Treatment, 105, 209–219.PubMedCrossRefGoogle Scholar
  41. 41.
    Ware, J. E., & Sherbourne, C. D. (1992). The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Medical Care, 30, 473–483.PubMedCrossRefGoogle Scholar
  42. 42.
    Schag, C. A. C., Heinrich, R. L., Aadland, R. L., & Ganz, P. A. (1990). Assessing problems of cancer patients: Psychometric properties of the Cancer Inventory of Problem Situations (CIPS). Health Psychology, 9, 83–102.PubMedCrossRefGoogle Scholar
  43. 43.
    Bjorner, J. B., Wallenstein, G. V., Martin, M. C., Lin, P., Piech Blaisdell-Gross, C. T., et al. (2007). Interpreting score differences in the SF-36 Vitality scale: Using clinical conditions and functional outcomes to define the minimally important difference. Current Medical Research and Opinions, 23, 731–739.CrossRefGoogle Scholar
  44. 44.
    Norman, G. R., Sloan, J. A., & Wyrwich, K. W. (2003). Interpretation of changes in health-related quality of life: the remarkable universality of half a standard deviation. Medical Care, 41, 582–592.PubMedGoogle Scholar
  45. 45.
    Revicki, D., Hays, R., Cella, D., & Sloan, J. (2008). Recommended methods for determining responsiveness and minimally important differences for patient-reported outcomes. Journal of Clinical Epidemiology, 61, 102–109.PubMedCrossRefGoogle Scholar
  46. 46.
    Sloan, J., Cella, D., & Hays, R. (2005). Clinical significance of patient-reported questionnaire data: Another step toward consensus. Journal of Clinical Epidemiology, 58, 1217–1219.PubMedCrossRefGoogle Scholar
  47. 47.
    Schwartz, A. L., Meek, P. M., Nail, L., Fargo, J., Lundquist, M., Donofrio, M., et al. (2002). Measurement of fatigue: determining minimally important differences. Journal of Clinical Epidemiology, 55, 239–244.PubMedCrossRefGoogle Scholar
  48. 48.
    American Joint Committee on Cancer. (2010). AJCC cancer staging handbook (7th ed.). Chicago: Author.CrossRefGoogle Scholar
  49. 49.
    Hand, D. J., & Taylor, C. C. (1987). Multivariate analysis of variance and repeated measures. London: Chapman and Hall.CrossRefGoogle Scholar
  50. 50.
    Davies, N., Gibbons, E., Mackintosh, A., Fitzpatrick, R. On behalf of the Oxford Patient-Reported Outcomes Measurement Group (2009). A structured review of patient-reported outcome measures (PROMs) for women with breast cancer. Oxford: University of Oxford.Google Scholar
  51. 51.
    Wilson, R. W., Hutson, L. M., & VanStry, D. (2005). Comparison of 2 quality-of-life questionnaires in women treated for breast cancer: The RAND 36-Item health survey and the functional living index–cancer. Physical Therapy, 85, 851–860.PubMedGoogle Scholar
  52. 52.
    Bower, J. E., Ganz, P. A., Desmond, K. A., Rowland, J. H., Meyerowitz, B. E., & Belin, T. R. (2000). Fatigue in breast cancer survivors: occurrence, correlates, and impact on quality of life. Journal of Clinical Oncology, 18, 743–749.PubMedGoogle Scholar
  53. 53.
    Merle, M. E. (1998). Correlates of fatigue in survivors of breast cancer. Cancer Nursing, 21, 136–142.CrossRefGoogle Scholar
  54. 54.
    Haghighat, S., Esmail Akbari, M., Holakouei, K., Rahimi, A., & Montazeri, A. (2003). Factors predicting fatigue in breast cancer patients. Supportive Care in Cancer, 11, 533–538.PubMedCrossRefGoogle Scholar
  55. 55.
    Day, R., Ganz, P. A., Costantino, J. P., Cronin, W. M., Wickerman, D. L., & Fisher, B. (1999). Health-related quality of life and tamoxifen in breast cancer prevention: A report from the national surgical adjuvant breast and bowel project P-1 study. Journal of Clinical Oncology, 17, 2659–2669.PubMedGoogle Scholar
  56. 56.
    de Jong, N., Courtens, A. M., Abu-Saad, H. H., & Schouten, H. C. (2002). Fatigue in patients with breast cancer receiving adjuvant chemotherapy: A review of the literature. Cancer Nursing, 25, 283–297.PubMedCrossRefGoogle Scholar
  57. 57.
    Lin, N. U., Vanderplas, A., Hughes, M. E., Theriault, R. L., Edge, S. B., Wong, Y.-N., et al. (2012). Clinicopathologic features, patterns of recurrence, and survival among women with triple-negative breast cancer in the national comprehensive cancer network. Cancer, 118, 5463–5472.PubMedCrossRefGoogle Scholar
  58. 58.
    Rakka, E. A., El-Sayed, M. E., Green, A. R., Lee, A. H. S., Robertson, J. F., & Ellis, I. O. (2007). Prognostic markers in triple-negative breast cancer. Cancer, 109, 25–32.CrossRefGoogle Scholar
  59. 59.
    Anderson, W. F., Chu, K. C., Chatterjee, N., Brawley, O., & Brinton, L. A. (2001). Tumor variants by hormone receptor expression in white patients with node-negative breast cancer from the surveillance, epidemiology, and end results database. Journal of Clinical Oncology, 19, 18–27.PubMedGoogle Scholar
  60. 60.
    Pilkonis, P. A., Choi, S. W., Reise, S. P., Stover, A. M., Riley, W. T., & Cella, D. (2011). Item banks for measuring emotional distress from the patient-reported outcomes measurement information system (PROMIS): Depression, anxiety, & anger. Assessment, 18, 263–283.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Angela M. Stover
    • 1
  • Bryce B. Reeve
    • 2
  • Barbara F. Piper
    • 3
  • Catherine M. Alfano
    • 4
  • Ashley Wilder Smith
    • 4
  • Sandra A. Mitchell
    • 4
  • Leslie Bernstein
    • 5
  • Kathy B. Baumgartner
    • 6
  • Anne McTiernan
    • 7
  • Rachel Ballard-Barbash
    • 4
  1. 1.Department of Health BehaviorUniversity of North Carolina - Chapel HillChapel HillUSA
  2. 2.Health Policy & ManagementUniversity of North Carolina at Chapel HillChapel HillUSA
  3. 3.National UniversitySan DiegoUSA
  4. 4.National Cancer InstituteFrederickUSA
  5. 5.City of Hope National Medical CenterDuarteUSA
  6. 6.University of LouisvilleLouisvilleUSA
  7. 7.Fred Hutchinson Cancer Research CenterSeattleUSA

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