Breast Cancer Research and Treatment

, Volume 105, Issue 2, pp 209–219 | Cite as

Psychological distress and fatigue predicted recurrence and survival in primary breast cancer patients

  • Mogens GroenvoldEmail author
  • Morten Aagaard Petersen
  • Ellen Idler
  • Jakob Bue Bjorner
  • Peter M. Fayers
  • Henning T. Mouridsen


This study examined whether psychological distress in newly diagnosed breast cancer patients was associated with their survival. We analyzed data from 1,588 breast cancer patients who filled in the EORTC QLQ-C30 questionnaire and the Hospital Anxiety and Depression Scale (HADS) 2 months after their primary operation. The median follow-up time was 12.9 years. Psychological distress (EORTC QLQ-C30 emotional function; HADS anxiety; HADS depression) and EORTC fatigue, physical function, and overall ratings were used to predict recurrence-free and overall survival, controlling for the known clinical and histopathological prognostic factors (biological model) using Cox multivariate regression analysis. Low levels of psychological distress (good EORTC emotional function) and low fatigue independently predicted longer recurrence-free and overall survival, controlling for biological factors. Lack of anxiety (HADS) also predicted longer recurrence-free survival. When added in combination to the biological model, fatigue remained a significant predictor of recurrence-free survival (P = 0.0004; risk ratio 1.32 (1.13–1.54)) and emotional function remained a significant predictor of overall survival (P = 0.0074; risk ratio 0.81 (0.70–0.95)). Low psychological distress and a low level of fatigue may cause a greater cancer resistance or may reflect underlying mental and physical robustness.


Breast neoplasms Survival Psychological distress Quality of Life Psychoneuroimmunology Prognostic factors 



The study was funded by the Danish Cancer Society (grant 94 150 01).


  1. 1.
    Spiegel D, Bloom JR, Kraemer HC, Gottheil E (1989) Effects of psychosocial treatment on survival of patients with metastatic breast cancer. Lancet 2:888–891PubMedCrossRefGoogle Scholar
  2. 2.
    Fawzy FI, Fawzy NW, Hyun CS, Elashoff R, Guthrie D, Fahey JL, Morton DL (1993) Malignant melanoma. Effects of an early structured psychiatric intervention, coping, and affective state on recurrence and survival 6 years later. Arch Gen Psychiatry 50:681–689PubMedGoogle Scholar
  3. 3.
    Cunningham AJ, Edmonds CV, Jenkins GP, Pollack H, Lockwood GA, Warr D (1998) A randomized controlled trial of the effects of group psychological therapy on survival in women with metastatic breast cancer. Psychooncology 7:508–517PubMedCrossRefGoogle Scholar
  4. 4.
    Edelman S, Lemon J, Bell DR, Kidman AD (1999) Effects of group CBT on the survival time of patients with metastatic breast cancer. Psychooncology 8:474–481PubMedCrossRefGoogle Scholar
  5. 5.
    Goodwin PJ, Leszcz M, Ennis M, Koopmans J, Vincent L, Guther H, Drysdale E, Hundleby M, Chochinov HM, Navarro M, Speca M, Hunter J (2001) The effect of group psychosocial support on survival in metastatic breast cancer. N Engl J Med 345:1719–1726PubMedCrossRefGoogle Scholar
  6. 6.
    Kissane DW, Love A, Hatton A, Bloch S, Smith G, Clarke DM, Miach P, Ikin J, Ranieri N, Snyder RD (2004) Effect of cognitive-existential group therapy on survival in early-stage breast cancer. J Clin Oncol 22:4255–4260PubMedCrossRefGoogle Scholar
  7. 7.
    Coates A, Thomson D, McLeod GR, Hersey P, Gill PG, Olver IN, Kefford R, Lowenthal RM, Beadle G, Walpole E (1993) Prognostic value of quality of life scores in a trial of chemotherapy with or without interferon in patients with metastatic malignant melanoma. Eur J Cancer 29A:1731–1734PubMedCrossRefGoogle Scholar
  8. 8.
    Kaasa S, Mastekaasa A, Lund E (1989) Prognostic factors for patients with inoperable non-small cell lung cancer, limited disease. The importance of patients’ subjective experience of disease and psychosocial well-being. Radiother Oncol 15:235–242PubMedCrossRefGoogle Scholar
  9. 9.
    Ganz PA, Lee JJ, Siau J (1991) Quality of life assessment. An independent prognostic variable for survival in lung cancer. Cancer 67:3131–3135PubMedCrossRefGoogle Scholar
  10. 10.
    Efficace F, Bottomley A, Coens C, van Steen K, Conroy T, Schoffski P, Schmoll H, Van Cutsem E, Kohne CH (2006) Does a patient’s self-reported health-related quality of life predict survival beyond key biomedical data in advanced colorectal cancer? Eur J Cancer 42:42–49PubMedCrossRefGoogle Scholar
  11. 11.
    Dharma-Wardene M, Au HJ, Hanson J, Dupere D, Hewitt J, Feeny D (2004) Baseline FACT-G score is a predictor of survival for advanced lung cancer. Qual Life Res 13:1209–1216PubMedCrossRefGoogle Scholar
  12. 12.
    Roychowdhury DF, Hayden A, Liepa AM (2003) Health-related quality-of-life parameters as independent prognostic factors in advanced or metastatic bladder cancer. J Clin Oncol 21:673–678PubMedCrossRefGoogle Scholar
  13. 13.
    McCarter H, Furlong W, Whitton AC, Feeny D, DePauw S, Willan AR, Barr RD (2006) Health status measurements at diagnosis as predictors of survival among adults with brain tumors. J Clin Oncol 24:3636–3643PubMedCrossRefGoogle Scholar
  14. 14.
    Sullivan PW, Nelson JB, Mulani PM, Sleep D (2006) Quality of life as a potential predictor for morbidity and mortality in patients with metastatic hormone-refractory prostate cancer. Qual Life Res 15:1297–1306PubMedCrossRefGoogle Scholar
  15. 15.
    Stockler MR, Osoba D, Corey P, Goodwin PJ, Tannock IF (1999) Convergent discriminitive, and predictive validity of the Prostate Cancer Specific Quality of Life Instrument (PROSQOLI) assessment and comparison with analogous scales from the EORTC QLQ-C30 and a trial-specific module. European Organisation for Research and Treatment of Cancer. Core Quality of Life Questionnaire. J Clin Epidemiol 52:653–666PubMedCrossRefGoogle Scholar
  16. 16.
    Maisey NR, Norman A, Watson M, Allen MJ, Hill ME, Cunningham D (2002) Baseline quality of life predicts survival in patients with advanced colorectal cancer. Eur J Cancer 38:1351–1357PubMedCrossRefGoogle Scholar
  17. 17.
    Coates A, Gebski V, Signorini D, Murray P, McNeil D, Byrne M, Forbes JF (1992) Prognostic value of quality-of-life scores during chemotherapy for advanced breast cancer. J Clin Oncol 10:1833–1838PubMedGoogle Scholar
  18. 18.
    Coates AS, Hurny C, Peterson HF, Bernhard J, Castiglione-Gertsch M, Gelber RD, Goldhirsch A (2000) Quality-of-life scores predict outcome in metastatic but not early breast cancer. International Breast Cancer Study Group. J Clin Oncol 18:3768–3774PubMedGoogle Scholar
  19. 19.
    Efficace F, Biganzoli L, Piccart M, Coens C, van Steen K, Cufer T, Coleman RE, Calvert HA, Gamucci T, Twelves C, Fargeot P, Bottomley A (2004) Baseline health-related quality-of-life data as prognostic factors in a phase III multicentre study of women with metastatic breast cancer. Eur J Cancer 40:1021–1030PubMedCrossRefGoogle Scholar
  20. 20.
    Kramer JA, Curran D, Piccart M, de Haes JC, Bruning P, Klijn J, Van Hoorebeeck I, Paridaens R (2000) Identification and interpretation of clinical and quality of life prognostic factors for survival and response to treatment in first-line chemotherapy in advanced breast cancer. Eur J Cancer 36:1498–1506PubMedCrossRefGoogle Scholar
  21. 21.
    Luoma ML, Hakamies-Blomqvist L, Sjostrom J, Pluzanska A, Ottoson S, Mouridsen H, Bengtsson NO, Bergh J, Malmstrom P, Valvere V, Tennvall L, Blomqvist C (2003) Prognostic value of quality of life scores for time to progression (TTP) and overall survival time (OS) in advanced breast cancer. Eur J Cancer 39:1370–1376PubMedCrossRefGoogle Scholar
  22. 22.
    Tross S, Herndon II J, Korzun A, Kornblith AB, Cella DF, Holland JF, Raich P, Johnson A, Kiang DT, Perloff M, Norton L, Wood W, Holland JC (1996) Psychological symptoms and disease-free and overall survival in women with stage II breast cancer. Cancer and Leukemia Group B. J Natl Cancer Inst 88:661–667PubMedCrossRefGoogle Scholar
  23. 23.
    Efficace F, Therasse P, Piccart MJ, Coens C, van Steen K, Welnicka-Jaskiewicz M, Cufer T, Dyczka J, Lichinitser M, Shepherd L, de Haes H, Sprangers MA, Bottomley A (2004) Health-related quality of life parameters as prognostic factors in a nonmetastatic breast cancer population: an international multicenter study. J Clin Oncol 22:3381–3388PubMedCrossRefGoogle Scholar
  24. 24.
    Lehto US, Ojanen M, Dyba T, Aromaa A, Kellokumpu-Lehtinen P (2006) Baseline psychosocial predictors of survival in localised breast cancer. Br J Cancer 94:1245–1252PubMedCrossRefGoogle Scholar
  25. 25.
    Goodwin PJ, Ennis M, Bordeleau LJ, Pritchard KI, Trudeau ME, Koo J, Hood N (2004) Health-related quality of life and psychosocial status in breast cancer prognosis: analysis of multiple variables. J Clin Oncol 22:4184–4192PubMedCrossRefGoogle Scholar
  26. 26.
    Watson M, Haviland JS, Greer S, Davidson J, Bliss JM (1999) Influence of psychological response on survival in breast cancer: a population-based cohort study. Lancet 354:1331–1336PubMedCrossRefGoogle Scholar
  27. 27.
    Watson M, Homewood J, Haviland J, Bliss JM (2005) Influence of psychological response on breast cancer survival: 10-year follow-up of a population-based cohort. Eur J Cancer 41:1710–1714PubMedCrossRefGoogle Scholar
  28. 28.
    Wulsin LR, Vaillant GE, Wells VE (1999) A systematic review of the mortality of depression. Psychosom Med 61:6–17PubMedGoogle Scholar
  29. 29.
    Idler EL, Benyamini Y (1997) Self-rated health and mortality: a review of twenty-seven community studies. J Health Soc Behav 38:21–37PubMedCrossRefGoogle Scholar
  30. 30.
    Bjorner JB, Kristensen TS, Orth-Gomér K, Tibblin G, Sullivan M, Westerholm P (1996) Self-rated health: a useful concept in research, prevention and clinical medicine. Swedish Council for Planning and Coordination of Research, StockholmGoogle Scholar
  31. 31.
    Rumsfeld JS, MaWhinney S, McCarthy M Jr, Shroyer AL, VillaNueva CB, O’Brien M, Moritz TE, Henderson WG, Grover FL, Sethi GK, Hammermeister KE (1999) Health-related quality of life as a predictor of mortality following coronary artery bypass graft surgery. Participants of the Department of Veterans Affairs Cooperative Study Group on Processes, Structures, and Outcomes of Care in Cardiac Surgery. JAMA 281:1298–1303PubMedCrossRefGoogle Scholar
  32. 32.
    Frasure-Smith N, Lesperance F, Juneau M, Talajic M, Bourassa MG (1999) Gender, depression, and one-year prognosis after myocardial infarction. Psychosom Med 61:26–37PubMedGoogle Scholar
  33. 33.
    Petticrew M, Bell R, Hunter D (2002) Influence of psychological coping on survival and recurrence in people with cancer: systematic review. BMJ 325:1066PubMedCrossRefGoogle Scholar
  34. 34.
    Danish Breast Cancer Cooperative Group (1989) DBCG-89. Program for treatment and follow-up of patients with primary, operable breast cancer [In Danish]. DBCG-Sekretariatet, CopenhagenGoogle Scholar
  35. 35.
    Groenvold M (1997) Quality of life in breast cancer adjuvant therapy: validation and pilot testing of a combination of questionnaires. Breast 6:97–107CrossRefGoogle Scholar
  36. 36.
    Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, Filiberti A, Flechtner H, Fleishmann SB, de Haes JCJM, Kaasa S, Klee M, Osoba D, Razavi D, Rofe PB, Schraub S, Sneeuw K, Sullivan M, Takeda F (1993) The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 85:365–376PubMedCrossRefGoogle Scholar
  37. 37.
    Fayers PM, Aaronson N, Bjordal K, Groenvold M, Curran D, Bottomley A and on behalf of the EORTC Quality of Life Group (2001) The EORTC QLQ-C30 scoring manual, 3rd edn. European Organization for Research and Treatment of Cancer, BrusselsGoogle Scholar
  38. 38.
    Zigmond AS, Snaith RP (1983) The Hospital Anxiety and Depression Scale. Acta Psychiatr Scand 67:361–370PubMedCrossRefGoogle Scholar
  39. 39.
    Hansen EJ (1986) Social classes in Denmark [In Danish]. Danish National Institute of Social Research, CopenhagenGoogle Scholar
  40. 40.
    Early Breast Cancer Trialists’ Collaborative Group (1998) Polychemotherapy for early breast cancer: an overview of the randomised trials. Lancet 352:930–942CrossRefGoogle Scholar
  41. 41.
    Herrmann C (1997) International experiences with the Hospital Anxiety and Depression Scale–a review of validation data and clinical results. J Psychosom Res 42:17–41PubMedCrossRefGoogle Scholar
  42. 42.
    Schmoor C, Schumacher M (1997) Effects of covariate omission and categorization when analysing randomized trials with the Cox model. Stat Med 16:225–237PubMedCrossRefGoogle Scholar
  43. 43.
    Garssen B, Goodkin K (1999) On the role of immunological factors as mediators between psychosocial factors and cancer progression. Psychiatry Res 85:51–61PubMedCrossRefGoogle Scholar
  44. 44.
    Holmes MD, Chen WY, Feskanich D, Kroenke CH, Colditz GA (2005) Physical activity and survival after breast cancer diagnosis. JAMA 293:2479–2486PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2006

Authors and Affiliations

  • Mogens Groenvold
    • 1
    • 2
    Email author
  • Morten Aagaard Petersen
    • 3
  • Ellen Idler
    • 4
  • Jakob Bue Bjorner
    • 5
  • Peter M. Fayers
    • 6
    • 7
  • Henning T. Mouridsen
    • 8
  1. 1.The Research Unit, Department of Palliative MedicineBispebjerg HospitalCopenhagenDenmark
  2. 2.Institute of Public HealthUniversity of CopenhagenCopenhagenDenmark
  3. 3.The Research Unit, Department of Palliative MedicineBispebjerg HospitalCopenhagenDenmark
  4. 4.Institute for Health, Health Care Policy, and Aging ResearchRutgers UniversityNew BrunswickUSA
  5. 5.National Institute of Occupational HealthCopenhagenDenmark
  6. 6.Department of Public HealthUniversity of Aberdeen Medical SchoolAberdeenUK
  7. 7.Unit of Applied Clinical Researchthe Norwegian University of Science and TechnologyTrondheimNorway
  8. 8.Department of Oncology ONKFinsen CentreCopenhagenDenmark

Personalised recommendations