Clinical Update - Breast Cancer
Clinical Update Issue 23 - May 2006 - ISSN 1328-9454 See previous editions
FATIGUE IN LONG-TERM BREAST CARCINOMA SURVIVORS
Commentary by Clinical Associate Professor David Goldstein
The article:
Bower JE, Ganz PA, Desmond KA et al. Fatigue in long-term breast carcinoma survivors: a longitudinal investigation. Cancer 2006;106(4):751–8Reviewer:
David Goldstein is a conjoint Clinical Associate Professor and senior staff specialist in the Department of Medical Oncology at the Prince of Wales Hospital in Sydney. He has an interest in cancer-related fatigue.
In this issue...
- Article summary
- What does this article add to existing clinical evidence in this area?
- How adequate was the methodology used in addressing the aims of the study?
- What are the implications of the study for clinical practice in Australia?
Summary
Abbreviations
Breast Cancer Prevention Trial (BCPT); Centre for Epidemiologic Studies – Depression Scale (CES-D); Confidence Interval (CI); Odds Radio (OR)
Study design
This article describes a longitudinal study in which 763 breast cancer survivors completed multiple questionnaires at two intervals, 1–5 and 5–10 years after diagnosis. The questionnaires included RAND SF-36, CES-D, BCPT Symptom Checklist, Fear of Recurrence Scale, demographic and medical data.
The primary aims of this study were to provide information on the prevalence and persistence of fatigue in long-term breast cancer survivors and to identify predictors of fatigue at 5–10 years after diagnosis. Predictors of fatigue that were considered included both demographic and medical conditions. Predictor variables were analysed by multivariate logistic regression models.
Findings
Prevalence & persistence:
- 35% of women were classified as fatigued at 1–5 years after diagnosis; 34% at 5–10 years after diagnosis.
- 21% of women were classified as fatigued at both assessment points.
Predictors of fatigue:
Characteristics of fatigued and nonfatigued women:
Demographic variables:
Income was the only demographic variable associated with fatigue, fatigued women reporting lower income than nonfatigued women (p=0.05).
Health conditions:
The following health conditions were more prevalent among fatigued women than nonfatigued women: diabetes (p=0.02); high blood pressure (p=0.005); heart problems (p=0.003); arthritis (p=0.02); depressive symptoms (p<0.0001); bodily pain (p<0.0001); hot flushes/night sweats (p=0.007).
Concurrent predictors of fatigue:
Fatigue was associated with:
- depressive symptoms (OR: 1.17; 95% CI: 1.13 to 1.21; p<0.0001)
- bodily pain (OR: 0.98; 95% CI: 0.97 to 0.98; p<0.0001) (NB Higher SF-36 scores indicate less pain)
- high blood pressure (OR: 1.80; 95% CI: 1.14 to 2.86; p<0.05).
Women were less likely to be fatigued if they received radiation treatment alone compared with radiation and chemotherapy (OR: 0.53; 95% CI: 0.31 to 0.89; p<0.05).
Longitudinal predictors of fatigue:
Fatigue was associated with:
- depressive symptoms (OR: 1.04; 95% CI: 1.01 to 1.06; p<0.01)
- high blood pressure (OR: 1.75; 95% CI: 1.08 to 2.81; p<0.05).
Women treated with radiation alone or chemotherapy alone were less likely to be fatigued than women treated with both radiation and chemotherapy (OR: 0.47; 95% CI: 0.27 to 0.80; p=0.005 and OR: 0.56; 95% CI: 0.32 to 0.98; p=0.04, respectively).
For both concurrent and longitudinal predictors of fatigue, when analysed by a multiple regression model, heart disease was found to be a significant predictor of fatigue while high blood pressure was not.
Conclusion
For some breast cancer survivors, fatigue continues to be a problem for many years after diagnosis. Several factors which may contribute to fatigue may be amenable to intervention.
What does this article add to existing clinical evidence in this area?
The increasing success of adjuvant treatment in improving outcomes for women with breast cancer has resulted in a renewed focus on the impact of treatment on long-term health. Increasing numbers of patients report prolonged periods of ill health after the end of therapy. Initially this was first characterised as treatment-related fatigue but reported with increasing frequency following treatment. The first cross-sectional studies identified up to 40% of women experiencing long-term disabling fatigue that interfered with normal activities. A syndrome similar to that of post-infectious chronic fatigue was identified and attempts made to define it [1,2].
One of the features of these initial reports was the absence of baseline measurements to demonstrate that a real change had occurred. Most recently, prospective studies have been reported which also show fatigue in 20% and 26% respectively up to 3 years post-treatment [3,4]. In addition the well-recognised incidence of depression was not always accounted for when reporting post-treatment fatigue rates [5].
This study represents a more measured approach with careful attempts to identify associated states that could account for fatigue symptoms but could be due to potentially treatable aetiology.
How adequate was the methodology used in addressing the aims of the study?
This study is important for its size, the care in identifying associated features and most important the duration of follow-up. It is a report of significant fatigue that persists unabated 4 to 10 years post-treatment. In the previous study report a cohort of 1957 women with breast cancer who had completed all therapy were surveyed at 1–5 years post-treatment and a prevalence of 30% was reported and a strong association with depression and other medical co-morbidities was identified [6].
In this report the same women were recontacted to participate in a follow-up assessment. The instruments used included a scale for assessing health-related quality of life (SF-36) which includes four items on fatigue, a depression scale (CES-D), a scale assessing menopausal symptoms and a fear of recurrence scale. Sixty-one percent of the 1336 women contacted responded. Of these, 763 had not had a recurrence and were analysed. Their demographics were similar to those reported by the non-responders at the previous contact. At the 5–10 year follow-up 34% of the women were classified as fatigued. Of these the majority were the same ones as previously reporting fatigue at the 1–5 year follow-up, but for 12% of women who had previously reported fatigue it had resolved and 13% of the women had become fatigued since the 1–5 year follow-up.
An association between fatigue and lower income, which has previously been reported in the non-malignant literature, was noted. Co-morbid medical conditions, such as diabetes, heart failure, hypertension and arthritis, were all co-associated as was depression and menopausal symptoms. Combined chemo-radiation was associated with a higher prevalence in multivariate analysis. Similarly pain, depression high blood pressure and arthritis were all predictors of fatigue. Baseline fatigue, depression, bodily pain and combined modality therapy were all longitudinal predictors of fatigue.
What are the implications of the study for clinical practice in Australia?
The study highlights that the majority of women treated for breast cancer do not experience long-term fatigue and that, of the significant minority who do, potentially treatable factors such as depression may allow for useful intervention. Screening for such factors in women reporting long-term fatigue and associated disability in terms of role functioning remains the first step in management. In addition, as stated in the article, there is a need for closer prospective assessment of patients to exclude baseline fatigue states not related to breast cancer or its treatment, to study the temporal nature of the severity of fatigue symptoms over time and to use more comprehensive fatigue inventories to better understand the dimensions of the experience.
A recent focus on cognitive function following breast cancer treatment showed potential resolution of identified problems with time [7]. In addition a recent small study identifies variable changes possibly existing before therapy as well as resolution of any changes over time for most women [8]. These recent studies suggest the need for more prospective long-term studies before concluding the true extent of either fatigue or cognitive changes as long-term major adverse outcomes of treatment.
References
- Cella D, Peterman A, Passik S, Jacobsen P, Breitbart W. Progress toward guidelines for the management of fatigue. Oncology (Huntington) 1998;12(11A):369–77
- Ahlberg K, Ekman T, Gaston-Johansson F, Mock V. Assessment and management of cancer-related fatigue in adults. Lancet 2003;362(9384):640–50
- Nieboer P, Buijs C, Rodenhuis S, et al. Fatigue and relating factors in high-risk breast cancer patients treated with adjuvant standard or high-dose chemotherapy: a longitudinal study. J Clin Oncol 2005;23(33):8296–304
- Andrykowski MA, Schmidt JE, Salsman JM, Beacham AO, Jacobsen PB. Use of a case definition approach to identify cancer-related fatigue in women undergoing adjuvant therapy for breast cancer. J Clin Oncol 2005;23(27):6613–22
- Bennett B, Goldstein D, Lloyd A, Davenport T, Hickie I. Fatigue and psychological distress – exploring the relationship in women treated for breast cancer. Eur J Cancer 2004;40(11):1689–95
- Bower JE, Ganz PA, Desmond KA, et al. Fatigue in breast cancer survivors: occurrence, correlates, and impact on quality of life. J Clin Oncol 2000;18:743–53
- Fan HG, Houede-Tchen N, Yi QL, et al. Fatigue, menopausal symptoms, and cognitive function in women after adjuvant chemotherapy for breast cancer: 1- and 2-year follow-up of a prospective controlled study. J Clin Oncol 2005;23(31):8025–32
- Jenkins V, Shilling V, Deutsch G, et al. A 3-year prospective study of the effects of adjuvant treatments on cognition in women with early stage breast cancer. Br J Cancer 2006;94:828–34
Editor: Dr Alison Evans, Program
Manager NBCC.
Editorial Committee: Mr Max Coleman, Mr John Collins,
Dr Sue-Anne McLachlan, Dr Sue Pendlebury, Dr Martin Stockler.
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