The results of this study of women with breast cancer extend findings on both inter-individual and diurnal variability in fatigue initially reported in a group of prostate cancer patients who underwent RT.13
Diurnal variability was evaluated in both studies to test the hypothesis that fatigue severity varies over the course of the day and may be influenced by different factors. Mean levels of morning (2.9) and evening (5.0) fatigue at the initiation of RT were in the moderate range.50,51
However, these levels of fatigue may be underestimates of the amount of fatigue women who are about to undergo RT experience because among the 61 patients who declined to participate in this study, the primary reason cited was being too overwhelmed with the experience of cancer. In addition, these baseline levels of morning and evening fatigue were higher than those reported by men with prostate cancer at the initiation of RT (i.e., 2.0 and 3.6, respectively).13
The incremental increases in evening and morning fatigue in this sample as a whole were modest but consistent with previous reports.4,15,16,18,23
However, the use of HLM, compared to more traditional statistical approaches (e.g., repeated measures analysis of variance) provided evidence of a large amount of inter-individual variability in baseline levels, as well as in the trajectories of evening and morning fatigue. In addition, these HLM analyses provide insights into which of these women with breast cancer were at increased risk for more severe and prolonged fatigue trajectories.
The estimated mean evening fatigue scores at the time of the simulation visit ranged from 0.2 to 8.2, which spans the mild to severe range.50,51
Consistent with previous reports that evaluated overall levels of fatigue during RT,4,15,16,18,23
mean evening fatigue scores increased gradually during RT and gradually declined following the completion of RT (). The predictors of baseline levels of evening fatigue included having children at home and higher CES-D scores. In addition, women who were employed showed a small but steady increase in evening fatigue over the six months of the study. As shown in , patients who were caring for children at home and those who reported higher levels of depressive symptoms had evening fatigue scores at the initiation of RT that were above the clinically significant level of 5.6.32,51
While previous reports have not examined the impact of caring for children on women’s level of fatigue during RT, the finding of increased fatigue in women who reported higher depression scores at the initiation of RT is consistent with two previous reports.17,20
However, the finding that being employed was a predictor of higher levels of evening fatigue is not consistent with a previous report that found that women who worked more hours reported lower fatigue severity scores.22
This inconsistency warrants consideration in future studies.
Taking care of children and working may represent important lifestyle factors that contribute to the development of fatigue in women who are receiving RT for breast cancer. While these factors were not identified as predictors of evening fatigue in men with prostate cancer,13
clinicians who care for women with breast cancer should assess for these factors and counsel patients about possible lifestyle modifications or the need for assistance while on treatment.
Estimated mean morning fatigue scores at the time of the simulation visit ranged from 0.0 to 7.5. In contrast to evening fatigue, morning fatigue scores decreased slightly during RT and then plateaued about two weeks after the completion of RT ().The predictors of higher baseline levels of morning fatigue were younger age, higher levels of sleep disturbance and trait anxiety, and lower BMI. Both younger age and higher levels of sleep disturbance were predictors of baseline levels of morning fatigue in men with prostate cancer who underwent RT.13
Of note, other cross-sectional studies of oncology patients have associated sleep disturbance52–54
and trait anxiety55
with higher levels of average fatigue.
At the time of the simulation visit, the mean sleep disturbance and anxiety scores were above the cutoffs for clinically significant levels of these two symptoms.35,51,56
In addition, as shown in , patients with higher levels of trait anxiety or sleep disturbance had morning fatigue scores at the initiation of RT that were above the clinically significant level of 3.2.32,51
These findings suggest that clinicians need to assess not only for fatigue but for anxiety and sleep disturbance in patients with breast cancer who undergo RT.
In terms of BMI being a predictor of baseline levels of morning fatigue, 4.1% of the women in this study were underweight and 37.8% had a BMI in the normal range. This finding warrants additional investigation because the data on the relationship between BMI and fatigue are inconclusive.18,57,58
The predictors of the trajectories of morning fatigue were co-morbidity and stage of disease. A higher number of co-morbidities was associated with higher levels of fatigue, which confirms findings from one study.52
While pretreatment with CTX was associated with higher levels of fatigue in some studies,15,21
but not in others,16
it was not a predictor of morning or evening fatigue in this study. However, in this study, advanced stage of disease may be a proxy for a higher level of treatment burden and/or an independent disease-related predictor of higher levels of fatigue. All of these predictors warrant investigation in future studies.
Diurnal variability in and different predictors for evening and morning fatigue suggest that different factors and different mechanisms underlie the development of fatigue. While morning fatigue appears to be more affected by biologic factors, evening fatigue appears to be more affected by behavioral factors. These data suggest that different interventions may be needed to reduce diurnal variations in fatigue.
Different predictors for fatigue were found for this cohort of women with breast cancer compared to a cohort of patients with prostate cancer who underwent RT.13
The patients with prostate cancer were more homogeneous in their clinical characteristics. All of these patients had localized prostate cancer, a low Gleason score, and a similar treatment history. The patients with breast cancer were more heterogeneous in terms of their disease stage and treatment history. These between group differences may explain why a number of biologic factors were related to fatigue in the breast cancer cohort but not in the prostate cancer cohort. While these findings warrant replication, they suggest that interventions for fatigue may need to be individualized based on the patient’s cancer diagnosis, as well as on personal and clinical characteristics.
Some limitations of this study include the relatively small sample size and the fact that most of the study participants were white and highly educated, which might limit the generalizability of the findings. The strengths of this study include the collection of longitudinal data on the trajectories of fatigue and the use of HLM to identify predictors of fatigue. The identification of factors that influence the development of fatigue may assist clinicians to identify patients at highest risk for the development of this deleterious symptom. In addition, these factors may be used in the development of intervention studies for cancer-related fatigue. However, additional research is warranted, with larger samples, to fully characterize those phenotypic and genotypic characteristics that influence patients’ experiences of fatigue during RT.