Fatigue Long-Lasting for Some Breast Cancer Survivors
A new study reports that although most breast cancer survivors do not experience long-term fatigue, one in five still feel tired up to ten years after diagnosis. Coexisting conditions, such as depression, pain, and arthritis, and type of treatment were associated with persistent fatigue.

Reporting Source: "Fatigue Persists in Some Breast Cancer Patients.", Jan. 11, 2006.
Primary Source : "Fatigue in Long-Term Breast Carcinoma Survivors." Cancer, Feb. 15, 2006; 106:.

Expert Comments by Lynne I. Wagner, PhD
Clinical Research Scientist
Assistant Professor
Northwestern University, Feinberg School of Medicine, Chicago, IL

By Mary Batten

This is a well-done study from researchers with a long track record of investigating quality of life for breast cancer survivors. It is also one of very few studies that have looked at fatigue in women who are more than five years past their cancer diagnosis. For the 21 percent of women in this study who were still tired up to ten years after diagnosis, fatigue was clearly a major problem. The good news from this study is that most breast cancer survivors did not experience such long-lasting fatigue. Findings that comorbid conditions such as depression, pain, arthritis, and high blood pressure are significant predictors of fatigue suggest targets for preventive interventions. This study, led by Julienne Bower, PhD, of the Cousins Center for Psychoneuroimmunology and the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, makes a valuable contribution to current knowledge about fatigue in breast cancer patients (Ref. 1). It also offers hope that treatments targeting co-existing conditions might relieve persistent fatigue or prevent it altogether.

Fatigue is the most common and debilitating side effect of cancer and its treatment (Ref. 2). Cancer-related fatigue is not the same as normal tiredness that most people feel from time to time. It is not relieved by getting extra hours of sleep, and it may last many months or even years after patients have finished treatment. Studies of breast cancer survivors have found that as many as one-third report significant fatigue within the first five years after diagnosis (Refs. 3-5). However, few studies have examined fatigue in long-term cancer survivors. The authors of this paper note that as breast cancer survivors are living longer, it is important to understand the long-term effects of treatment on quality of life.

The authors previously reported on fatigue in their study population at the 1-5-year assessment point (Ref. 3). At that time, approximately one-third of breast cancer survivors reported significant fatigue. Depression and pain were the major factors related to fatigue. The current study assessed fatigue in the same group of women at 5-10 years after diagnosis.

The Study
What Was Being Studied?
The prevalence and persistence of fatigue in long-term, disease-free breast cancer survivors; and factors that predict fatigue at 5-10 years after diagnosis.

How Was Information Gathered?
In 1994-1997, almost two thousand women in Los Angeles, CA, and Washington, DC, were recruited to participate in a study of health-related quality of life in the first five years after breast cancer diagnosis. The study group consisted of 1957 women who had been diagnosed with early-stage breast cancer between one and five years earlier, were disease-free, and had completed all cancer treatment other than tamoxifen. In 1998, the researchers got back in touch with women who were at least five years out from diagnosis and asked whether they would participate in a follow-up assessment. A total of 763 breast cancer survivors agreed to be part of this long-term follow-up. Each study participant completed several questionnaires designed to evaluate physical, emotional, and social well-being, including energy level, bodily pain, depression, and fear of recurrence.

Most breast cancer survivors did not experience long-term fatigue. In the 1-5-year study, 35 percent of the women were classified as fatigued. There was little change in the 5-10-year follow-up, with 34 percent classified as fatigued. In each follow-up assessment, a minority of patients (21 percent) reported significant fatigue. Interestingly, 12 percent scored in the fatigued range at baseline and in the nonfatigued range at the 5-10-year follow-up; 13 percent scored in the nonfatigued range at baseline and in the fatigued range at follow-up.

Factors associated with long-term fatigue were depression and other comorbid, or coexisting, conditions, including high blood pressure, heart disease, pain, and arthritis. The association with depression was so strong that the researchers emphasized the need for a careful assessment of depression in cancer survivors who report problems with fatigue (Ref. 1).

Patients treated with both radiation and chemotherapy were more likely to suffer long-term fatigue than were patients treated with either radiation or chemotherapy alone.

By Lynne I. Wagner, PhD
Clinical Research Scientist, Assistant Professor
Northwestern University, Feinberg School of Medicine
303 East Chicago Ave., Chicago, IL 60611-3008

This was a longitudinal study and the design was very solid. It's challenging to track people down and get a decent response rate. I was impressed with the 61-percent participation rate. In following the sample five and ten years later, these researchers really made a contribution in terms of looking at fatigue over time.

I was particularly interested in the rates of people who were fatigued at the first assessment and what happened in terms of their fatigue over time, as well as people who were not fatigued initially and how they fared over time with regard to fatigue. What they found was that basically, if you're fatigued earlier on, then you're much more likely to have fatigue later on as well. Knowing specifically what happens to those groups, as opposed to taking a cross-sectional look just to see how many people are fatigued at any given time, can really help to tailor interventions during or immediately after treatment for those who are at greater risk for having fatigue five to ten years later.

It makes sense that other conditions like depression and pain seem to go along with fatigue. As we better understand symptom clusters and the possible role of cytokines, it is becoming increasingly clear that people who are struggling with fatigue are also struggling with other things as well. Cytokines are proteins that the body uses to send signals and they are involved in the inflammation and immune process and in the development of new blood cells. Cytokines have been implicated in cancer-related fatigue, possibly in depression and possibly also in cognitive dysfunction.

We don't yet have a clear picture of how much fatigue is related to the cancer and how much is due to treatment. This article makes the point that the women who had multimodal treatment - both chemotherapy and radiation - had higher levels of fatigue. They were at greater risk for having fatigue long-term than women who underwent radiation alone. This finding suggests that chemotherapy plays a role in cancer-related fatigue. However, women who received both chemotherapy and radiation may be different from those who received radiation alone in a way that makes it more likely that will experience fatigue.

With respect to interventions that might relieve or prevent fatigue, these researchers suggested that perhaps treatment for depression may help fatigue. But we know from Dr. Gary Morrow's study (Ref 6) that paroxetine (Paxil) versus placebo did not improve participants' fatigue levels. It helped depression but the fatigue levels were still the same between groups. If you read this article and didn't know about the Morrow study, then this article would suggest that maybe if you take an SSRI for depression, then you won't be as much at risk down the road for fatigue. However, a clinical trial has shown that's not the case; and that really underscores the importance of randomized phase III trials in symptom management to evaluate interventions for fatigue.

The area of fatigue intervention that has received the most support is regular exercise. Exercise doesn't necessarily mean going to the gym for three hours or running 10 miles. For a person who has a sedentary lifestyle, even bumping up their physical activity with walking for 15 minutes a couple of times a week will help. Exercise helps depression and pain management as well. It's ironic that as recently as the late 1990s, oncologists' most frequent recommendation for relieving fatigue was bed rest. Clearly that's only going to make the fatigue more profound. We know this from studies such as those of Andrea Barsevick, a PhD nurse who does a lot of fatigue research (Refs. 7-8). Other people as well have conducted exercise intervention studies and, as more and more of these studies (are published), and they report positive results, we can become increasingly confident in that conclusion.

I think this study underscores the urgent need for randomized clinical trials to evaluate treatment interventions to alleviate fatigue. I would like to see treatment interventions that are evaluated by solid scientific design because there's a risk, and we've seen this happen with methylphenidate (Ritalin), that when people hear anecdotally that something might work, they run out and try it. Then you have difficulty conducting a) a placebo-controlled trial because everybody wants the treatment. They don't want the risk of receiving a placebo. However, we truly need these trials to advance the science in this area and ultimately to help patients who have fatigue.

1. Bower JE, Ganz PA, Desmond KA, et al. "Fatigue in Long-Term Breast Carcinoma Survivors." Cancer, Feb. 15, 2006; 106.
2. Lawrence DP, Kupelnick B, Miller K, et al. "Evidence Report on the Occurrence, Assessment, and Treatment of Fatigue in Cancer Patients." Journal of the National Cancer Institute Monograph 2004; 40-50.
3. Bower JE, Ganz PA, Desmond KA, et al. "Fatigue in Breast Cancer Survivors: Occurrence, Correlates, and Impact on Quality of Life." Journal of Clinical Oncology 2000; 18:743-753.
4. Lindley C, Vasa S, Sawyer WT, Winer EP. "Quality of Life and Preferences for Treatment Following Systemic Adjuvant Therapy for Early-Stage Breast Cancer." Journal of Clinical Oncology 1998; 16:1380-1387.
5. Servaes P, Verhagen S, Bleijenberg G. "Determinants of Chronic Fatigue in Disease-Free Breast Cancer Patients: a Cross-Sectional Study>" Annals of Oncology 2002; 13:589-598.
6. Morrow GR, Hickok JT, Roscoe JA, et al. "Differential Effects of Paroxetine on Fatigue and Depression in a Randomized, Double-Blind Trial from the University of Rochester Cancer Center Community Clinical Oncology Program." Journal of Clinical Oncology, Dec. 15, 2003; 21:4635-41.
7. Barsevick AM, Dudley W, Beck S, et al. "A Randomized Clinical Trial of Energy Conservation for Cancer-Related Fatigue." Cancer 2004; 100:1302-1310.
8. Mock V, Atkinson A, Barsevick A, et al. "Cancer-Related Fatigue Clinical Practice Guidelines in Oncology." Journal of the National Comprehensive Cancer Network 2003; 1:308-331.

Internet Sources
Breast Cancer Survivors Fatigued: Study
ABC Online, Jan. 10, 2006

Breast Cancer Survivors Plagued with Fatigue, Jan. 10, 2006

Fatigue Persists for Some Breast Cancer Patients, Jan. 11, 2006

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