Departments of 1 Health Care Studies, Section of Nursing Science and 2 Methodology and Statistics, Universiteit Maastricht, Maastricht; 3 Department of Internal Medicine, Section of HaematologyOncology, University Hospital Maastricht, Maastricht, The Netherlands; 4 School of Nursing & Faculty of Medicine, American University of Beirut, Lebanon
* Correspondence to: N. de Jong, MSc, RN, Universiteit Maastricht, Department of Health Care Studies, Section of Nursing Science, P.O. Box 616, 6200 MD Maastricht, The Netherlands. Tel: +31-43-388-1827; Fax: +31-43-388-4162; Email: n.dejong{at}zw.unimaas.nl
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Abstract |
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Patients and methods: In a prospective cohort study a sample of 157 patients with breast cancer was interviewed at the first, third and fifth cycle of adjuvant chemotherapy as well as 4 and 12 weeks after completion of adjuvant chemotherapy. Patients were treated with standard adjuvant chemotherapy, either a doxorubicin containing schedule or CMF (cyclophosphamide, methotrexate and fluorouracil). The psychological dimensions of fatigue were measured by the Multidimensional Fatigue Inventory. A linear multilevel model was used for analysing the courses.
Results: The course of mental fatigue and motivation were not affected by the type of chemotherapy. The course of mental fatigue and motivation varied, but seemed to be stable during the treatment of chemotherapy. After the completion of chemotherapy, a weak improvement was seen. Relatively many patients experienced depressive symptoms during the study. These symptoms were correlated with both dimensions of fatigue. At all measurements mental fatigue was influenced by type of operation where women with a mastectomy were significantly more mentally fatigued than women that had undergone a lumpectomy, but nevertheless they were significantly more motivated to start any activity. Age, marital status, number of treatments and the interval between the operation and the first treatment of chemotherapy also seemed to be important determinants.
Conclusions: An unequivocal pattern of mental fatigue and reduced motivation during as well as after adjuvant chemotherapy was not found. Depressive symptoms were definitely related to these variables. Type of operation had a significant impact on mental fatigue and motivation to start any activity. Health care providers should be aware of the high rate of patients who experience depressive symptoms during and after the treatment of chemotherapy. Further research should include the trajectory preceding adjuvant chemotherapy and a longer study period afterwards. Moreover, the exact influence of the variables age, marital status, number of treatments and the interval between the operation and the first treatment of chemotherapy on fatigue is unclear and needs further study.
Key words: adjuvant chemotherapy, breast cancer, mental fatigue, motivation
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Introduction |
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Breast cancer has been the most frequently occurring malignancy in women since the early 1990s in the Netherlands [3]. A large subset of these patients receives adjuvant chemotherapy as part of the standard treatment. The course of fatigue in these patients has also hardly been examined. In a recent literature review [2
], high and fluctuating prevalence rates of fatigue in breast cancer patients have been found not only during but also after adjuvant chemotherapy. The intensity of fatigue seems to be stable throughout the treatment cycles. After the treatment of adjuvant chemotherapy, patients still experience fatigue, but it is unknown whether this fatigue can be regarded as normal fatigue. The influence of different factors on the course of fatigue is unclear and less well studied [2
]. The impact of different chemotherapy regimens on the course of fatigue is not unequivocal, but seems to be an important factor. Berger and Walker [4
] found recently that chemotherapy protocols that contain intravenous doxorubicin were directly associated with higher fatigue at the first treatment. They studied 60 women during the first three cycles of adjuvant breast chemotherapy [4
]. De Jong et al. [5
] reported that the course of general and physical fatigue during and after chemotherapy treatment was significantly different for the CMF group (combination chemotherapy with cyclophosphamide, methotrexate and fluorouracil), compared with a doxorubicin group. After the start of chemotherapy, a direct increase in fatigue is seen in the doxorubicin group, whereas the increase in the CMF group does not show until after the fifth cycle of chemotherapy.
Fatigue is associated with various symptoms [2]. There is evidence for a relationship between fatigue and the severity of psychological symptoms [2
]. The loss of a breast can have devastating psychological effects on women [6
]. Depressive symptoms are a common and disruptive problem for cancer patients [7
]. That fatigue and depression are related is beyond doubt but the interpretation of this relation is, however, complicated [8
]. The symptoms of fatigue and depression overlap. In addition, fatigue is one of the key symptoms of depression and may be the result of depressed mood. On the other hand, a person who continuously perceives his or her energy as insufficient may become depressed. Cancer fatigue and depression may co-occur without having a causal relationship, because they can both originate from the same pathology [8
].
The course of fatigue in breast cancer patients receiving adjuvant chemotherapy with regard to psychological aspects, such as cognitive functioning, concentration ability, mental effort and mood-state, is less frequently studied. Cimprich [9] has reported a decline in the capacity for attention and concentration in women undergoing treatment for breast cancer in the initial phases of illness.
In a recent study by De Jong et al. [5], the course of general and physical fatigue, as a function of chemotherapy (CMF group versus doxorubicin group), was studied in 157 breast cancer patients undergoing adjuvant chemotherapy. These two dimensions of fatigue were measured by the Multidimensional Fatigue Inventory (MFI-20) [5
]. This study is part of this large-scale examination and will describe, also using the MFI-20, the psychological dimensions of fatigue: mental fatigue and reduced motivation. Cognitive symptoms such as having difficulties concentrating are included in the scale mental fatigue [10
]. Lack of motivation to start any activity is covered by the scale reduced motivation [10
]. In this study, these two subscales were examined, because only these two subscales relate to psychological aspects of fatigue and both may be related in a unique way to quality of life compared with the other subscales of the MFI-20. Depression was measured by the Center for Epidemiological Studies Depression Scale (CES-D) [11
]. This scale measures depressive feelings that may result from experiencing a particular incident [12
].
As a result of the absence of longitudinal studies on the course of dimensions of fatigue conducted so far, the purpose of this study was to examine the course of mental fatigue and reduction in motivation during (two or three measurement points) as well as after (two measurement points) adjuvant chemotherapy.
In this study, we test two hypotheses. The first is mainly based on a literature review [2]: the intensity of mental fatigue and reduction in motivation remains stable during the treatment of chemotherapy and changes in a positive direction after completion. The impact of different chemotherapy regimens, like doxorubicin-containing regimens, on the course of fatigue is unclear and will therefore be further investigated in this study. The second hypothesis holds that, during as well as after adjuvant chemotherapy, fatigue and depressive symptoms are related.
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Patients and methods |
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Before the first cycle of adjuvant chemotherapy and after checking the inclusion criteria, the oncologist or the oncology nurse introduced the study to the patient with written information describing the purpose and procedure of the investigations. The oncologist or the oncology nurse contacted the principal investigator of this study after obtaining written informed consent. The principal investigator and a properly trained assistant interviewed the participants. All local medical ethical committees of the participating centres had approved the study.
Data collection
Data were collected, using the Multidimensional Fatigue Inventory (MFI-20) [13], five times except when receiving the CA (cyclophosphamide and doxorubicin) treatment, in which case participants were interviewed only four times. Patients had the first interview at the start of chemotherapy, the second at the third cycle and the third at the fifth cycle except for the CA regimen, where the third interview was omitted. The last two interviews were held 4 and 12 weeks after the last cycle. The first three interviews took place directly before, during or after infusion in the hospital. The interviews after the last cycle were done by telephone. The medical data were retrieved from charts after the interviews.
Operationalisation of variables
The intensity of fatigue. Fatigue was assessed by a 20-item questionnaire, the Multidimensional Fatigue Inventory (MFI-20) [13]. This self-report instrument, especially designed for cancer patients, consists of five scales based on different dimensions: general fatigue, physical fatigue, reduced activity, reduced motivation and mental fatigue. Each scale consists of four statements. The score for each scale was calculated as the sum of the scores of the four statements, for which high scores indicate more subjective fatigue. Statements should be answered with respect to the last days. Data for all subscales were collected. This study will focus on the results of two scales mental fatigue and reduced motivation. Cognitive symptoms such as having difficulties concentrating are included in the scale mental fatigue [10
]. Lack of motivation to start any activity is covered by the scale reduced motivation [10
]. The items of these subscales are presented in Table 1.
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Patients in this study were asked to rate, in an interview, their fatigue as experienced during the previous 2 weeks. A period of 2 weeks was chosen to obtain a more stable measure of the experienced fatigue between chemotherapy cycles. Instead of presenting the items in a self-report questionnaire, the items were administered in a face-to-face interview, since this took less time of the respondents. Another reason for administering the scales in a face-to-face interview was that there was a closer contact between the interviewer and patient. The personal attention of the interviewer was thought to be more motivating for respondents to continue participating in the study.
Depressive symptoms. The Center for Epidemiological Studies Depression Scale (CES-D) [11] was used to measure depressive symptoms. This self-report scale, administered as a structured interview in this study, contains 20 items selected from the previously validated scale of depression. Patients indicated how often within the last 2 weeks they experienced the symptoms, responding rarely or none of the time (0); some or little of the time (1); occasionally or a moderate amount of time (2); and most or all of the time (3). The range of scores is 0 to 60, with higher scores indicating more symptoms. The cut-off score for a depressive syndrome is 16.
The CES-D has been tested in healthy subjects, cancer patients, myocardium infarct patients and students. The internal consistency was good and varied between 0.79 and 0.92 [12]. In another study, the psychometric properties of CES-D were assessed for both women undergoing treatment for breast cancer and for women with no history of cancer. Here, also, good internal consistencies were found, with alpha coefficients greater than 0.85 [7
].
Treatment of adjuvant chemotherapy. Patients received one of the following adjuvant treatments: CEF (cyclophosphamide, 4-epi-doxorubicin and 5-fluorouracil) every 21 days, CAF (cyclophosphamide, doxorubicin and 5-fluorouracil) every 21 days, 4-epi-doxorubicin every 28 days (on days 1 and 8), 4-epi-doxorubicin/taxotere with the first three cycles every 28 days (on days 1 and 8) and the last three cycles every 21 days, CA (cyclophosphamide and doxorubicin) every 21 days and CMF [cyclophosphamide, methotrexate (oral administration from day 1 to day 14 or intravenous) and 5-fluorouracil] every 28 days (on days 1 and 8). Most regimens consisted of six cycles except the CA regimen which consisted of four cycles.
In this study, two groups were compared: the doxorubicin group (CEF, CAF, 4-epi-doxorubicin, 4-epi-doxorubicin/taxotere and CA) and the CMF group. The participating hospitals based the choice for either schedule on their current practice. The involvement of different adjuvant chemotherapy regimens in the doxorubicin group made it possible to create a sizeable sample in a relatively short period of time.
Stage of breast cancer. The anatomic extent of breast cancer was described using the TNM (tumournodemetastasis) clinical classification [15].
Type of operation. In this study, patients underwent a mastectomy or a lumpectomy with or without lymph nodes excision. In the analyses, two groups were compared because of the small sizes of the other groups: (1) mastectomy with lymph nodes excision, and (2) lumpectomy with lymph nodes excision. During the study period, no reconstructive surgery was done.
Statistical analyses
It was statistically tested whether there were differences in patient characteristics between the CMF group and the doxorubicin group.
The reliability of the MFI-20 and the CES-D was examined by calculating Cronbach's . This coefficient of internal consistency was calculated for each measurement point.
The course of mental fatigue, as well as motivation and dependency on the type of treatment of adjuvant chemotherapy, were analysed with a linear multilevel model using the MLwiN program (version 1.10.0006) [16]. The data consist of a series of repeated measurements nested within hospitals and individual subjects. The data, which have a hierarchical nature, may be characterised by dependencies between units at lower levels of the hierarchy. In this case, multilevel analysis is an appropriate technique [17
]. Before the main analyses were executed, a PP-plot of the residuals at the individual level was made to check the normality assumption of multilevel analysis.
In the analyses concerning the effect of chemotherapy regimen on the course of fatigue, dummy variables were included to represent several measurement points. When the first measurement is taken as a reference, changes relative to the baseline measurement are analysed. The effect of chemotherapy on the course of fatigue was represented by interaction terms between these dummy variables and a binary variable chemotherapy. To correct for possible confounding factors in this analysis, several covariates were added: age, marital status, having children, education, having a job, type of operation, stage of breast cancer, haemoglobin level (measured in mmol/l) before the first treatment of chemotherapy, the number of days between the operation and the first treatment of chemotherapy, the number of treatments at each measurement point and radiotherapy. For the covariate radiotherapy, three different variables were used: a variable indicating whether a patient had received radiotherapy at any point of measurement, the number of days of radiotherapy the patient had had at the time of measurement and the number of days between the last day of radiotherapy and the time of measurement. Also these covariates were included as interaction terms with the dummy variables representing the time points. In this way, possible differences in patient characteristics between the chemotherapy groups are corrected for.
A multi-collinearity analysis was completed to determine whether independent variables were strongly associated with each other.
Stepwise deletion took place in which non-significant covariates were deleted. A significance level of 0.05 was used. The least significant covariate, with significance level above 0.05 was deleted first. A new analysis was done, without this particular covariate, after which the least significant covariate was again deleted, provided that its significance level was above 0.05. This process continued until all covariates with significance level above 0.05 were deleted. For this model, the effect of the variable treatment of adjuvant chemotherapy was examined. For the final model, fatigue scores, which are differences relative to baseline and are also adjusted for differences between the chemotherapy groups, can be calculated. These will be denoted as adjusted baseline differences.
Finally, correlations were also calculated between depressive symptoms and the subscale mental fatigue as well as depressive symptoms and the subscale reduced motivation to examine their relationship.
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Results |
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Sample characteristics
The characteristics of the patients who were excluded from the study (n=18) were not available. Demographic and medical characteristics of the included patients are shown in Table 2. Forty-six patients (29%) had received the CMF treatment, the remainder had received one of the chemotherapies covered by the doxorubicin group. There were two characteristics on which the groups differed: age and having a job. Patients in the doxorubicin group were significantly (t=2.133; P=0.035) older than patients in the CMF group. The mean age was 48.2 years (SD = 9.0) in the doxorubicin group and 45.0 years (SD = 7.9) in the CMF group. Significantly (2(1)=4.768, P=0.034) fewer patients in the doxorubicin group had a job compared with the CMF group. Details on the total number of chemotherapy treatments are shown in Table 3.
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Normality and multicollinearity
A PP-plot of the residuals at the individual level was made to check the normality assumption. The PP-plot shows that residuals at this level were normally distributed.
None of the independent variables was very strongly associated with another independent variable (correlations always lower than 0.2) indicating that multi-collinearity was not a problem for the analysis.
Course of two psychological dimensions of fatigue
The course of fatigue was studied by analysing separately the results of two scales of the MFI-20 corresponding to the different dimensions that could be distinguished: mental fatigue and reduced motivation. In Figure 1, raw mean scores of both subscales are presented to give a first impression of the course of the two dimensions of fatigue. Both courses seemed to be relatively stable during the study period. A specific description of both courses is given next.
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The variable interval between operation and first treatment of chemotherapy was categorised into the groups: 1 to 25 days (n=46), 26 to 50 days (n=97), and 51 days or more (n=14). When combining all variables, the subgroups were too small to carry out separate analyses for each resulting stratum. Consequently, stratification only took place for each variable separately that interacted with the variable measurement points. By investigating the time effects in this way for each stratum, the averaged effects were examined, where the other two variables that interact with measurement points were averaged across.
The course of mental fatigue for the different groups that were distinguished with respect to the variable interval between operation and first treatment of chemotherapy, is displayed in Figure 2. The level of mental fatigue seemed to be higher in those with a larger interval between operation and first treatment of chemotherapy. The subgroup whose interval was 51 days or more was too small to warrant a reliable analysis. For the group 1 to 25 days there was a decrease in the mental fatigue from the first measurement occasion onwards. The difference in mental fatigue between consecutive measurement points turned out not to be significant. There was, however, a significant decrease between measurements 1 and 4 (2(1)=4.678, P <0.05) and measurements 1 and 5 (
2(1)=6.349, P <0.05). After the last chemotherapy treatment, patients experienced significantly less mental fatigue than at the start.
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For the variable number of treatments of chemotherapy, only the groups with four (n=21) and six (n=118) treatments were large enough for reliable analyses. Figure 3 shows the development of mental fatigue for both groups. Note that the group with four treatments did not have any observations at measurement point 3. For this group, none of the pairwise comparisons between measurements occasions were significant. There was mainly a decrease in mental fatigue for the group with six treatments. However, only the consecutive measurement occasion 4 and measurement occasion 5 differed significantly (2(1)=5.661, P <0.05). Furthermore, it was noticeable that there was a significant decrease between measurements 1 and 5 (
2(1)=3.975, P <0.05). In this subgroup too, mental fatigue was also significantly diminished after the last chemotherapy treatment.
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Course of reduced motivation
The course of reduction in motivation during the study was not significantly different for the CMF and the doxorubicin groups, which means an equality in the changes of motivation in both chemotherapy groups during the whole study.
The final model contains a significant interaction between the measurement occasions and marital status (2(12)=24.236, P <0.05). This indicates that the course of reduced motivation during the study was different for married women, single women, divorced women and widows. It is impossible to examine all courses statistically because of the small sample sizes. Only the sample with married women was large enough to examine further. Figure 4 displays the course of reduced motivation for married women. This is conspicuously similar to the curve of mental fatigue for married women. As in the course of mental fatigue for married women, results show no significant differences between consecutive measurement points. Considering consecutive measurement points, the degree of motivation of the married women remains stable. Nevertheless, a significant difference was found between measurement occasion 3 and measurement occasion 5 (
2(1)=3.961, P <0.05). Married women were significantly more motivated at measurement 5 than at measurement 3. The mental fatigue experienced, on the other hand, was not significantly different between these two measurements points.
Of the other covariates considered, there were significant effects of type of operation (2(1)=136.640, P <0.01) and the number of treatments of chemotherapy (
2(2)=8.876, P <0.05). Patients who underwent a lumpectomy reported significantly more reduced motivation than those who underwent a mastectomy. Furthermore, the total number of chemotherapy treatments had a significantly negative effect on the reduced motivation (
2(1)=3.881, P <0.05). The motivation of women who received in total more treatments is significantly higher.
Results with respect to depressive symptoms
Table 5 contains the results for the CES-D. At each measurement point, about 20% of the sample had a score higher than the cut-off point 16 and was depressed.
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Discussion |
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In this study, the following two hypotheses are examined. (1) The intensity of mental fatigue and reduction in motivation remains stable during the treatment of chemotherapy and changes in a positive direction after completion. The impact of different chemotherapy regimens, like doxorubicin-containing regimens, on the course of fatigue is unclear and is investigated in this study. (2) Fatigue and depressive symptoms during as well as after receiving adjuvant chemotherapy are related. Below, the conclusions with respect to the hypotheses are discussed.
Course of the two psychological dimensions of fatigue
Neither the course of mental fatigue nor the course of motivation were affected by type of chemotherapy. In other words, the extent of mental fatigue as well as the motivation in the CMF group and the doxorubicin group were the same. De Jong et al. [5] reported in another study that the course of general and physical fatigue was significantly different for these chemotherapy groups. Apparently, the difference in the chemical composition of the chemotherapies only has an effect on the physical part of fatigue.
The course of mental fatigue, on the other hand, was affected by the interval between operation and first treatment of chemotherapy, number of treatments as well as marital status. The subgroups created for each of these variables were too small to carry out separate analyses for each resulting stratum. Analyses were done examining the course of fatigue by averaging across the strata defined by other interacting covariates. This, however, did not give insight into the exact courses of fatigue for each of the different groups that should be distinguished. In most of the analyses, we see a stability of mental fatigue during the treatment of adjuvant chemotherapy, with a significant improvement in the last phase of the study. The hypothesis that the intensity of the dimensions is stable during the treatment of adjuvant chemotherapy and changes positively after completion is therefore supported. Although the course of motivation was affected by marital status and could only be described for married women, a similar tendency was seen. It should be noted that mental fatigue and reduction in motivation show a similar pattern across time which may be explained by both aspects reflecting the psychological side of fatigue. This finding additionally motivates presenting the results of these two dimensions of fatigue in one study.
An explanation for the stability during the treatment of chemotherapy could be that there is an increase in mental fatigue directly after hearing the diagnosis. Mental fatigue increases immediately, because of worries or anxiety about the recovery process or the treatment route and the motivation to start any activity might reduce. A recent study [18] in breast cancer patients partly supports this argument. The authors of this study found that cognitive fatigue was predicted by anxiety and pain [18
]. In another study, a high prevalence of fatigue (77%) was found before primary surgery [19
]. Cimprich [9
] has demonstrated a decline in the capacity for attention and concentration in women undergoing treatment for breast cancer in the initial phases of illness. Another reason for the increased fatigue in patients before the start of chemotherapy is the lingering physical and psychological stress associated with having recently undergone breast cancer surgery [20
]. Patients with a short interval between the operation and the first treatment of chemotherapy could experience a heightened level of fatigue before the start of chemotherapy, which can actually only decrease. A final reason might be a shift in the internal norm of the experience of these dimensions of fatigue of the patient. This process of changing one's internal standard is called response shift [21
]. Further research, in which the period preceding chemotherapy is also examined, must be done.
After the treatment of chemotherapy, mental fatigue diminished and motivation increased, but not all changes turn out to be significant. In fact, in some cases the extent of the two dimensions of fatigue at the last measurement was equal to the fatigue experienced during the treatment of chemotherapy.
The time after the last treatment might be too short to find a change in fatigue that is large enough to result in a significant effect in the statistical analysis. It might be that patients needed longer to recover from the treatments or had to cope with the treatment process they had undergone. Budin [22] reported that the course of psychosocial adjustment confronting woman with breast cancer can be described as a series of phases associated with the clinical course of the treatment. A particularly stressful period for some breast cancer patients could be the period after completion of chemotherapy, when the woman continues recuperation from initial treatment and begins extensive reorganization and resumption of previous activities and roles. Beisecker et al. [23
] reported that many patients experience ambivalence at the end of chemotherapy. They are pleased to be finished, but they are afraid they should keep doing something to prevent a recurrence. A limitation of this study is the absence of a healthy control group with which to compare. In the study it is therefore unclear whether the findings at the last measurement can be regarded as normal or not.
Determinants of the course of fatigue
The course of mental fatigue is influenced by type of operation. Women undergoing a mastectomy were significantly more mentally fatigued than women that had undergone a lumpectomy. Cimprich [24] found a similar result. She concluded that older age and more extensive surgery increase the likelihood of loss of attention due, in part, to greater risk of attentional fatigue. Attentional fatigue manifests itself as a decreased capacity to concentrate or direct attention in daily life activities. The meaning of attentional fatigue is similar to both dimensions of fatigue investigated in this study. Cimprich [24
] studied 74 women newly diagnosed with stage I or II breast cancer. Data were obtained at about 12 days before and 15 days after breast-conserving surgery or mastectomy. The reason for an association here is probably not only the extent of the surgery, but also the psychological impact of it. The loss of a breast can have devastating psychological effects on women [6
]. Research shows that women undergoing breast conservation or post-mastectomy procedures have better outcomes on selected psychosocial and quality-of-life measures than those who underwent a mastectomy [25
]. Surgery of the breast is still seen as a negative aspect of the body image [25
, 26
]. In this context, the influence of the type of operation on the course of motivation is therefore not expected and hard to explain. In this study, women who underwent a mastectomy reported significantly less reduction in motivation than women undergoing a lumpectomy.
There is also an influence of age on the course of mental fatigue, meaning that older patients reported significantly less mental fatigue than younger patients. Results of other studies show that younger women with breast cancer have more severe emotional distress than older women. Loss of a breast or poor breast appearance would be more distressing to women whose youth gives them high expectations for physical beauty [27]. Another reason may be that younger women had the responsibility of caring for their families and young children [28
]. Besides, older women have normally experienced more setbacks and therefore probably can cope better with it. Ongoing research, involving coping strategies, must be done.
Furthermore, the total number of chemotherapy treatments has a significant effect on the course of motivation. The motivation of women who received in total more treatments is significantly less reduced. An explanation for this finding might be that these patients got an extra boost to go for it.
The following covariates did not influence the course of the psychological dimensions of fatigue: having children, education, having a job, stage of breast cancer, haemoglobin level before the first treatment of chemotherapy and the variables with respect to radiotherapy. Bower et al. [29] found no relation between educational attainment and fatigue nor between employment status and fatigue. Other studies [20
, 30
, 31
] support the absence of finding any relationship between stage of disease and fatigue. Okuyama et al. [31
] reported that radiotherapy was not correlated with fatigue. None of these studies however examined the course of psychological aspects of fatigue, and the covariates used are defined differently.
Depressive symptoms and fatigue
It should be noted that the mean scores for the CES-D, given the range of possible scores, are rather low. However, at each measurement point, a relatively large group, that is about 20% of the sample, can be classified as suffering from a depressive syndrome.
A limitation of the CES-D is the validity of the cut-off point (depressed or not depressed) [12]. In a study involving 50 patients with depression and 150 healthy men and women, the cut-off score seems to be adequate for diagnosis of depression [32
]. Results of another study showed that the standard cut-off score appears valid, but inefficient for depression screening in low-income women attending primary-care clinics [33
]. Best cut-off scores above 20 were found in studies with different populations [34
, 35
]. Apparently, different populations have different cut-off scores. In a study in cancer patients and in healthy individuals from the general population, findings support the use of a sumscore based on the 16 negatively formulated CES-D items as a more valid measure of depressive symptomatology [36
]. The use of the cut-off score of 16 in cancer patients therefore seems to be legitimate. Further research, involving examination of the sensitivity and specificity, is needed to determine the most accurate cut-off score in breast cancer patients.
Fatigue and depressive symptoms are positively related during the whole study period, which supports the second hypothesis. In their study, Visser and Smets [8] found a moderate relation. Other studies [29
, 31
, 37
, 38
] in breast cancer patients receiving chemotherapy also showed a positive relationship between depression and fatigue.
The findings of this study clarify the psychological dimensions of fatigue. A limitation of this study might be selection bias. The sample of patients who declined further participation is very small, but it is not known how many patients refused to participate in the study at the stage in which the oncologist or the oncology nurse introduced the study to the patients.
Note that patients were interviewed five times in a relatively short period of time. At each interview, they had to answer the same questions, which might cause a certain habituation. Moreover, different interview styles, i.e. face to face interviews and interviews by phone, were carried out. The internal consistency of both ways of administering the questionnaire are good. What is unknown is the way these methods may bias the results obtained on respondents' fatigue. A final remark concerning the period of study is the absence of a clear positive effect at the end of the study. The duration of the study might be too short to see any effect. The same can be said concerning the trajectory preceding adjuvant chemotherapy. Measurements somewhat longer before the start of chemotherapy may highlight increases in both mental fatigue and reduced motivation due to chemotherapy.
In summary, from this study we may conclude that no unequivocal pattern of mental fatigue and motivation is found, though there is a tendency for stability during the study with a potential decline in mental fatigue and an increase in motivation after completion of chemotherapy. In general, relatively many patients experienced depressive symptoms during the study. Health care providers should pay attention to the possibility of patients experiencing depressive symptoms. Recognition and treatment of these symptoms can influence the course of the chemotherapy treatment positively, as well as the quality of life during and after the treatment of chemotherapy. Based on the results of this study, more specific information about the psychological part of fatigue can be given to breast cancer patients receiving adjuvant chemotherapy. Behaviour related to this psychological part, like having difficulties concentrating and lack of motivation to start any activity, should be recognised by health care providers. Recognition and talking about these disturbances can be of value for the patient.
The depressive symptoms are definitely related to the psychological dimensions of fatigue. The psychological dimensions of fatigue are affected by type of operation. Age, marital status, number of treatments and the interval between the operation and the first treatment of chemotherapy also seem to be important determinants. Further research, involving these determinants must be carried out.
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Acknowledgements |
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Received for publication June 25, 2004. Revision received November 3, 2004. Accepted for publication November 12, 2004.
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References |
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