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Fatigue, anxiety and depression overrule the role of oncological treatment in predicting self-reported health complaints in women with breast cancer compared to healthy controls

The Breast, August 2016, Pages 100 - 106

Abstract

Background

Women with breast cancer often attribute their health problems as side effects caused by oncological treatments. The aim of the study was to examine and compare self-reported health complaints (SHC) in postmenopausal patients with breast cancer to healthy controls.

Method

Women with breast cancer (N = 196) filled in 5 questionnaires 1–2 years after surgery; SHC Inventory, Functional Assessment of Cancer Therapy-Endocrine Subscale (FACT-ES), Fatigue – Functional Assessment of Cancer Therapy-Fatigue subscale (FACIT-F), Fatigue Visual Analog Scale (Fatigue VAS), and Hospital Anxiety and Depression Scale (HADS). Controls comprised 101 blood donors who reported on the questionnaires except for HADS. Bonferroni adjustment and p < 0.0017 was considered statistically significant for SHC Inventory, p < 0.05 for the remaining questionnaires.

Results

The patients, mean age 58.0 (SD 9.5), reported significantly more self-reported health complaints, whereof 6 of 29 complaints were significantly elevated compared to the controls, mean age 57.0 (SD 5.8) (p < 0.001). HADS scores in patients fell into normal range, mean 6.3 (SD 5.7). A subgroup of 48 patients experienced more frequent and severe symptoms in all the questionnaires compared to the remaining 148 patients, and the 101 controls. Among the patients, fatigue, anxiety and depression explained 49% of the total variance in self-reported health complaints (p ≤ 0.001).

Conclusion

Most women with breast cancer (76%) reported health complaints equal to the healthy controls. Fatigue, anxiety and depression, not oncological treatments, were significant predictors for the complaints.

Highlights

  • Fatigue, anxiety and depression predict self-reported health complaints in women with breast cancer.
  • Seventy-six percent of Norwegian women with breast cancer reported similar health complaints compared to healthy controls.
  • The SHC Inventory is a suitable tool for examining self-reported health complaints in women with breast cancer.

Keywords: Self-reported health complaints, Postmenopausal symptoms, Breast cancer, Oncological treatments.

Abbreviations: SHC - Subjective Health Complaints, FACT-ES - Functional Assessment of Cancer Therapy-Endocrine Subscale, FACIT-F - Fatigue – Functional Assessment of Cancer Therapy-Fatigue subscale, Fatigue VAS - Fatigue Visual Analog Scale, HADS - Hospital Anxiety and Depression Scale, FEC - Flourouracil + Epirubicin + Cyclofosfamid, SD - Standard Deviation, OR - Odds Ratio, CI - Confidence Intervals, Tam - Tamoxifen, Al - Aromatase Inhibitor.

Introduction

Adjuvant chemotherapy and endocrine therapy, i.e. tamoxifen (Tam) and aromatase inhibitors (AIs) prevent recurrence in estrogen receptor-positive breast cancer patients [1]. Treatment works by blocking the stimulatory effect of estrogen on the estrogen receptor level, or by suppressing the total body estrogen levels [1], both creating a menopausal transition [1]. Early menopause caused by chemotherapy has been reported in 40% of 40 year old women, and close to 100% in women after the age of fifty [2]. Women who become post-menopausal at a younger age are more likely to have bothersome symptoms compared to older women [3].

Side effects of hormone blockade are typically those that accompany onset of menopause; heat flushes, sleep disturbance, fatigue, vaginal dryness and depression [4], [5], and [6]. Fatigue is described as an unusual or extreme sensation of tiredness that is not easily overcome by rest or sleep, and afflicts the whole human being [7]. Attacks of fatigue that recur or persist for more than 6 months are classified as chronic [7] and [8]. Prevalence of cancer-related fatigue is approximately 60%–90%, and may persist for months to years after the completion of therapy [8]. Interrupted sleep is also a substantial problem in breast cancer patients [9]. In addition, between 30% and 50% of cancer patients report anxiety and depression [9], which may increase mortality risk when elevated symptoms [10]. Individuals with concomitant depression have a greater non-adherence to endocrine treatment compared to patients without depression [11]. Many healthy postmenopausal women often report health complaints like the patients [3]. However, Amir et al. [12], found that the breast cancer treatments, like chemotherapy and endocrine therapy, may lead to a higher risk of developing the same health complaints. Though, the physiology of the menopause is complex, and may vary considerably both among patients and healthy women [13] and [14].

Self-reported health complaints, are defined as symptoms or complaints that, despite thorough examination, cannot be fully explained [15]. The Subjective Health Complaints Inventory (SHC Inventory) is a validated instrument commonly used in different populations and countries, examining self-reported health complaints during the last month [15] and [16]. Self-reported health complaints are very common, and the most frequently reported complaints are muscle and joint pain, gastrointestinal problems, tiredness and sleep disorders [15] and [17]. Studies suggest that subgroups of breast cancer patients report several postmenopausal complaints [13] and [18]. In clinical practice, patients with breast cancer often wonder whether the symptoms are a result of treatment or due to aging. However, there are few studies examining these complaints in women with breast cancer compared to postmenopausal healthy controls.

The objectives of this study were; (1) examine the validity of SHC Inventory in women with breast cancer, (2) compare self-reported health complaints in patients with breast cancer, 1–2 years after surgery, to healthy controls, (3) identify differences in self-reported health complaints in the patient group, and (4) factors that explain the variance in these complaints.

Material and methods

Participants

Women with breast cancer were recruited from two university hospitals between 2012 and 2013 [19]. The study population were consecutive patients receiving curative breast cancer treatment (surgery, chemotherapy, radiation, and/or endocrine therapy). Demographic information like age, body-mass index (BMI), marital status, and education was obtained, and medical records were used to confirm cancer-related data. 209 patients, 1–2 years (median 18 months) after surgery responded to 5 questionnaires about health problems. Thirteen patients dropped out due to; long travel distance (n = 8), unknown reasons (n = 4), and dead (n = 1). As a result, 196 (94%) patients were included. After curative treatment, none of the patients self-reported regained menstruation, and consequently, they were all in a postmenopausal state.

The controls were 315 female blood donors coming to a university hospital during the spring of 2014. The women were given information about the study and asked to participate by filling in 4 of the 5 questionnaires, and giving the same demographic information as the patients. All the controls accepted the participation. Those 101, who self-reported a postmenopausal state, were included in this study.

The patients and controls were Norwegian women more than 18 years of age.

Measures

SHC Inventory was the core instrument to examine subjective health complaints, and is not previously tested in a breast cancer population. Therefore, three validated breast cancer- and one generic questionnaire were used to substantiate the results in the SHC Inventory. The instrument measures 29 subjective, somatic and psychological complaints experienced during the last month, and has a satisfactory validity and reliability [16]. Severity of each complaint is rated on a 4-point Likert scale; 0 = “no” complaints to 3 = “severe complaints” (range 0–87). The questionnaire evaluates five domains; musculoskeletal pain (headache, neck pain, upper back pain, low back pain, arm pain, shoulder pain, migraine, and leg pain, range 0–24), “pseudoneurology” (tiredness, sleep problems, anxiety, sadness/depression, extra heartbeats, heath flushes, and dizziness, range 0–21), gastrointestinal problems (gas discomfort, stomach discomfort, diarrhea, constipation, gastritis/ulcer, heartburn, and stomach pain, range 0–21), allergy (allergies, breathing difficulties, eczema, and asthma, range 0–15) and flu (cold/flu and coughing, range 0–6) [16]. In a previous study using SHC Inventory, 86% from the general population and 96% of the healthy controls [17] reported a score below 20, which was considered as normal. We therefore used a SHC-score of 20 as cut-off value to dichotomize patients into subgroups.

Functional Assessment of Cancer Therapy – Endocrine Subscale, version 4 (FACT-ES) contains 19 statements examining self-reported menopausal and sexual symptoms related to breast cancer endocrine therapy during the last week. A license had to be obtained before using the FACT-ES (http://www.facit.org/). The scores range from 0 = “not at all” to 4 = “very much”, range 0–76. According to the guidelines, all the questionnaires are drafted in a way that higher scores represent improved quality of life [20], therefore, higher scores must represent fewer symptoms. When translating the FACT-ES from English to Norwegian, the FACIT Translation Project Team's methodology was followed [21]. Cronbach's alpha for the Norwegian version of FACT-ES was 0.86 in patients, and 0.83 in controls.

Functional Assessment of Cancer Therapy – Fatigue Subscale, version 4 (FACIT-F), is a validated self-assessment scale consisting of 13 items measuring physical and mental fatigue affecting daily life during the last week [22]. Each item is rated on a 5-point scale (0 = “not at all” to 4 = “very much”, range 0–52) and higher scores represent fewer symptoms [22]. Cronbach's alpha in the patients and controls were 0.84 and 0.81 respectively.

Fatigue Visual Analog Scale (Fatigue-VAS) is a 100 mm line where the far left is 0 = “no problems with fatigue and exhaustion”, and the far right is 10 = “so much fatigue and exhaustion that is possible to experience”, during the last week [23]. The scale examines the intensity of fatigue reported by the patients during the clinical investigation.

HADS is a self-assessment mood scale consisting of 14 items, 7 for HADS-A (anxiety) and 7 for HADS-D (depression) [24]. Each item is rated from 0 = “not present” to 3 = “maximum”. The scale has been extensively validated [25] and [26]. Two groups of psychopathology are defined; case level anxiety (HADS-A ≥ 8) and case level depression (HADS-D ≥ 8), which is based on accepted cut-off values on HADS [25].

Statistical analysis

Statistical analysis was performed using numbers (n) and percentages (%), mean and standard deviation (SD), and Odds ratios (OR) with 95% confidence intervals (95% CI). Statistical significance of differences in continuous variables was tested by the Mann–Whitney U test, and in categorical variables by Chi square tests. The one-way analysis of variance (ANOVA) was used to determine the significant difference between the means of three independent groups. Correlations were analyzed using the Spearman rank correlation coefficient. All tests were two-sided with a statistically significant p value of <0.05. Bonferroni adjustment [27] was conducted to counteract the problem of multiple comparisons in post hoc tests on the SHC Inventory items, and p < 0.0017 was considered as statistically significant. Influence of age, oncological treatments, anxiety and depression, and fatigue (independent variables) on self-reported health complaints (dependent variable) was study by multiple regression analysis. Data were analyzed using SPSS 22.0 for Windows (Armonk, NY: IBM Corp.).

Results

Patient characteristics

There were no significant differences between patients and controls; information about the study participants is summarized in Table 1.

Table 1

Sample characteristics (N, %) of breast cancer women compared to controls.

 

Patients (N = 196) Controls (N = 101) p-Value
Age in years (mean, SD) 57.7 (SD 9.5) 57.5 (SD 5.8) 0.510a
Time since diagnosis, months 18 (12–24)
Body-mass index (BMI)
Healthy weight (18.5–24.9 kg/m2) 97 (49) 49 (49) 1.000b
Overweight (25–29.9 kg/m2) 78 (40) 43 (43) 0.311b
Obese (30+ kg/m2) 21 (11) 7 (7) 0.519b
Marital status
Married or living with a partner 142 (72) 79 (78) 0.399b
Single 13 (7) 5 (5) 0.620b
Divorced 28 (14) 16 (16) 0.728b
Widow 13 (7) 1 (1) 0.068b
Education
Primary school, 10 years 101 (52) 42 (42) 0.086b
Secondary school, 11–14 years 75 (38) 46 (46) 0.321b
College/university 20 (10) 13 (13) 0.218b
Type of surgery
Mastectomy 116 (60)
Lumpectomy 52 (27)
Reconstruction 60 (52)
Treatment
cFEC 30 (15)
cFEC + Taxan 85 (43)
Herceptin 30 (15)
Radiation therapy 129 (66)
Endocrine treatment 138 (70)
 Aromatase Inhibitor (Letrozole) 84 (42)
 Tamoxifen 54 (28)

a Mann–Whitney U test.

b Chi-Square test.

c 5 Flourouracil + Epirubicin + Cyclofosfamid.

Patients reported outcomes

SHC Inventory; The subgroup scores of SHC Inventory correlated significantly with self-reported postmenopausal complaints and fatigue in both patients and controls (p = 0.01) (Table 2). Cronbach's alpha in patients and controls were 0.89 and 0.87, respectively.

Table 2

Correlation (Spearman correlation coefficient r) of the SHC Inventory subgroups, postmenopausal complaints, and fatigue in breast cancer patients (N = 196) and controls (N = 101).

 

SHC Inventory FACT-ES FACIT-F Fatigue-VAS
Patients Controls Patients Controls Patients Controls
Gastrointestinal complaints 0.48 0.48 0.44 0.40 0.43 0.39
Musculoskeletal complaints 0.50 0.51 0.51 0.41 0.39 0.39
Pseudoneurology 0.73 0.72 0.64 0.60 0.47 0.58
Allergy 0.24 0.10 0.41 0.18 0.31 0.26
Flu 0.19 0.11 0.22 0.22 0.19 0.24

All the correlations are significant at the p = 0.01 level.

Totally, the SHC Inventory severity score was significantly higher among the patients (mean, SD) 14.3 (SD 10.1) than the controls, 7.6 (SD 7.1) p < 0.001. Four patients (2%) and 10 controls (10%) did not report any subjective health complaints (p = 0.66). Six of 29 health complaints in the instrument were reported by significantly more patients than controls (Table 3).

Table 3

Number (%) of individuals with health complaints in patients compared to controls with Odds ratio (OR) and 95% confidence intervals (95% CI).

 

SHC Inventory Patients (N = 196) Controls (N = 101) OR (95% CI) p-Valuea
Musculoskeletal pain
 Headache 94 (48) 38 (38) 1.5 (0.9–2.5) 0.1090
 Low back pain 102 (52) 38 (38) 1.8 (1.1–2.9) 0.0200
 Neck pain 84 (43) 39 (39) 1.2 (0.7–1.9) 0.5347
 Shoulder pain 103 (53) 36 (36) 2.0 (1.2–3.3) 0.0061
 Arm pain 98 (50) 29 (29) 2.5 (1.5–4.2) 0.0020
 Upper back pain 65 (33) 23 (23) 1.7 (1.0–2.9) 0.0612
 Leg pain during physical activity 90 (46) 18 (18) 3.9 (2.2–7.0) <0.0001
 Migraine 20 (10) 12 (12) 0.8 (0.4–1.8) 0.6946
Pseudoneurology
 Tiredness 149 (76) 41 (41) 4.6 (2.8–7.8) <0.0001
 Sleep problems 124 (63) 40 (40) 2.6 (1.6–4.3) 0.0001
 Anxiety 39 (20) 12 (12) 1.8 (0.9–3.7) 0.1040
 Sadness/depression 66 (34) 17 (17) 2.5 (1.4–4.6) 0.0025
 Extra heartbeats 65 (33) 20 (20) 2.0 (1.1–3.6) 0.0208
 Heat flushes 135 (69) 43 (43) 1.8 (1.3–2.6) <0.0001
 Dizziness 73 (37) 14 (14) 3.7 (2.0–7.0) <0.0001
Gastrointestinal problems
 Gas discomfort 101 (52) 47 (47) 1.2 (0.8–2.0) 0.4628
 Stomach discomfort 41 (21) 7 (7) 3.5 (1.5–8.2) 0.0024
 Diarrhea 65 (33) 14 (14) 3.1 (1.6–5.8) 0.0004
 Constipation 47 (24) 10 (10) 2.9 (1.4–6.0) 0.0047
 Gastritis, ulcer 6 (3) 1 (1) 3.2 (0.4–26.6) 0.4291
 Heartburn 60 (31) 17 (17) 2.2 (1.2–4.0) 0.0116
 Stomach pain 46 (23) 15 (15) 1.8 (1.0–3.3) 0.0664
Allergies
 Allergy 41 (21) 16 (16) 1.4 (0.8–2.7) 0.3515
 Breathing difficulties 29 (15) 7 (7) 2.3 (1.0–5.5) 0.0600
 Eczema 42 (22) 8 (8) 3.2 (1.4–7.1) 0.0030
 Asthma 17 (9) 8 (8) 1.1 (0.5–2.6) 0.3499
 Chest pain 42 (21) 7 (7) 3.7 (1.6–8.5) 0.0018
Flu
 Cold/flu 60 (28) 19 (19) 1.9 (1.1–3.4) 0.0372
 Coughing 48 (25) 11 (11) 2.7 (1.3–5.4) 0.0056

a P-values were calculated by Chi-Square test, and p < 0.0017 was considered to be statistically significant.

The Bonferroni test attempts to prevent data from incorrectly appearing to be statistically significant by lowering the alpha value, and p values were represent in bold.

One hundred and forty-eight (76%) patients and 96 (95%) controls reported a SHC Inventory score < 20. The 48 (24%) patients with a SHC Inventory score ≥ 20 reported significantly more subjective health complaints, 28.0 (SD 9.5) compared to the patients, 9.9 (SD 5.3), and the controls, 6.4 (SD 4.7) with a score < 20 (all p < 0.0001).

There were no significant differences between the two groups of patients except for more self-reported health complaints among those with a SHC Inventory score ≥ 20 (Table 4).

Table 4

Sample characteristics (N, %) and results of SHC Inventory subgroups in two groups of patients.

 

SCH Inventory SHC score ≥ 20 (N = 48) SHC score < 20 (N = 148) p-Value
Age in years (mean, SD) 58.4 (SD 9.8) 55.8 (SD 8.0) 0.069a
Healthy weight (18.5–24.9 kg/m2) 21 (44) 75 (50) 0.407b
Overweight (25–29.9 kg/m2) 19 (40) 52 (35) 0.730b
Obese (30+ kg/m2) 8 (17) 19 (13) 0.541b
Married or living with a partner 36 (75) 108 (73) 0.705b
Surgery type
Lumpectomy 11 (23) 43 (30) 0.461b
Mastectomy 28 (58) 88 (59) 1.000b
Treatment
Chemotherapy 28 (58) 87 (59) 1.000b
Radiation 29 (60) 92 (62) 1.000b
Herceptin 5 (10) 23 (15) 0.483b
Endocrine therapy 36 (75) 102 (69) 0.360b
SHC Inventory (subgroups)
Musculoskeletal complaints 10.0 (SD 4.1) 3.1 (SD 2.7) <0.001a
Gastrointestinal complaints 5.5 (SD 3.5) 1.6 (SD 1.6) <0.001a
Pseudoneurology 8.7 (SD 2.8) 3.9 (SD 2.7) <0.001a
Allergy 2.4 (SD 2.0) 0.7 (SD 1.1) <0.001a
Flu 1.3 (SD 1.5) 0.6 (SD 1.0) <0.001a

a Mann–Whitney U.

b Chi-Square test.

FACT-ES; The 48 patients with a SHC Inventory score ≥ 20 reported significantly more menopausal symptoms, 52.0 (SD 10.3) compared to the patients, 63.9 (SD 7.9), and the controls, 69.1 (SD 6.5), with a score < 20 (all p < 0.0001). Comparing patients and controls with a SHC Inventory score < 20, the patients reported significantly more menopausal symptoms like heat flushes (64% vs 45%), mood fluctuations (47% vs 17%) and being irritable (44% vs 24%) (p < 0.001). The remaining 16 symptoms did not differ between these patients and controls.

Comparing patients on hormone therapy, Tam (N = 54) and AI (N = 84), with those receiving no such therapy (N = 58), the first group reported significantly more symptoms 60.1 (SD 10.2) and 63.2 (SD 9.4), respectively, compared to the second group, 65.6 (SD 8.0) (p = 0.005). Heat flushes were the most frequently reported problem in 20 (37%) patients in the Tam group, and joint pain in 22 (26%) patients in the AI group.

FACIT-F and Fatigue-VAS; Patients (N = 48) with SHC Inventory score ≥ 20 reported more fatigue, 32.8 (SD 9.7), than the patients (N = 148), 43.8 (SD 7.1), and controls, 46.0 (SD 6.7), with a score < 20 (all p < 0.001). The results of the Fatigue-VAS, reported in the same order as the above, were 51.6 (SD 23.0), 23.9 (SD 21.5), and 12.6 (SD 19.9) (p < 0.001), respectively.

HADS; Total score for patients was 6.3 (SD 5.5), for HADS-A; 4.1 (SD 3.4) and HADS-D; 2.4 (SD 2.6). Among the 48 patients reporting a SHC Inventory score ≥ 20, 29 (60%) had a case level of anxiety and depression, 10.2 (SD 5.9). The HADS-A scores correlated significantly with the scores of the item “anxiety” in the SHC Inventory, r = 0.48, as did the HADS-D scores and the scores of “depressed mood”, r = 0.58 (all p < 0.0001).

In the multiple regression analysis, oncological treatment for breast cancer explained <1% of the variance in the SHC Inventory, (p = 0.48). Adding anxiety and depression to the model increased the amount of explained variance to 32% (p < 0.001). In the final model (including fatigue and age) the amount of explained variance in subjective health complaints increased to 49%, where anxiety and depression, and fatigue were the significant predictors (p = 0.001) (Table 5).

Table 5

Multiple regression analysis of Subjective Health Complaints Inventory in breast cancer patients (N = 196).

 

Subjective Health Complaints Inventory
R2 Ba p-Value
bChemotherapy, Radiation, Herceptin, cTam or dAI 0.004 0.482
Chemotherapy, Radiation, Herceptin, Tam or AI, HADS 0.318 <0.001
Chemotherapy, Radiation, Herceptin, Tam or AI, HADS, FACIT-F, Age 0.489 <0.001
Chemotherapy −0.057 0.358
Radiation 0.005 0.920
Herceptin −0.004 0.948
Tam or AI 0.062 0.263
HADS 0.313 0.001
FACIT-F −0.491 0.001
Age −0.011 0.847

a Beta.

b Taxan and/or FEC (5 Flourouracil + Epirubicin + Cyclofosfamid).

c Tamoxifen.

d Aromatase Inhibitor.

Bold values report the ANOVA results for the three models.

Abbreviations:

Discussion

The aim of the study was to examine self-reported health complaints in women with breast cancer compared to healthy controls. Among five questionnaires, SHC Inventory was the core instrument, where the five subgroups correlated significantly with the other instruments used. In addition, an acceptable Cronbach's alphas indicate satisfactory validity of the instrument. Leg pain, interrupted sleep, heath flushes, tiredness, dizziness, and diarrhea were reported by significantly more by patients than controls. In patients, fatigue, anxiety and depression were significant predictors for the complaints.

Seventy percent of patients were on endocrine therapy, which is known to provide more severe heat flushes and tiredness than a naturally postmenopausal status [13]. The users of Tam reported significantly more severe heat flushes than the users of AI, or those on no endocrine treatment, which is in accordance to previous studies [12] and [28]. Leg pain is associated with Taxan treatment [29], and more patients than controls reported this complaint. Joint pain, not caused by arthritis, is a documented side effect associated with AI therapy [4] and [28]. The conclusions of such studies, however, are inconsistent [30] and [31]. This may be the case for joint pain on AI treatment as well. In this study, 26% of the patients receiving AI treatment reported severe joint pain compared to 10% in previous studies [32] and [33]. In healthy postmenopausal women however, joint- and leg pain are reported by 33–50% [34], indicating that these problems may be associated with age as well as with the breast cancer treatment. Previously findings using the SHC Inventory have revealed that the general population report more health complaints compared to healthy controls like nurses working in the theater [17]. It is therefore conceivable that, comparing breast cancer patients to controls from the general population may have made the differences even smaller than shown in this study. Due to coping strategies, quality of life, and last but not least, adherence to adjuvant therapy, this knowledge may be important information to women with breast cancer.

Some studies have found that many patients with breast cancer under-report health problems after surviving the main treatment for the disease [35], [36], and [37]. The explanation may be that the patients believe this is something they have to live with [36]. There may also be patients that do not perceive more health complaints after breast cancer treatment. Improvement in surgical procedures may have decreased for example arm and shoulder pain [38], and more individualized treatment may have reduced the perception of health complaints in general. Previously, most of the patients have reported high score on social support and satisfaction with the information about their disease [19], which may contribute positively to the present results.

Irritable bowel syndrome (IBS) is one of the most common functional disorders of the lower gastrointestinal tract [39], with a peak among middle-aged women [40]. Among the patients, diarrhea was their main gastrointestinal problem. It might be questioned whether the patients represent women suffering from IBS before the breast cancer diagnosis. Also, the illness may have increased during treatment, or debuted due to treatment. A recent study by Russo et al. [41] concludes that breast cancer patients undergoing FEC60 and reporting diarrhea, show alteration in the intestinal permeability, which is one of the hypotheses on etiology of IBS [42]. The authors propose further studies investigating differences in luminal and microbiotas conditions in breast cancer patients, corresponding with research in IBS patients [41] and [42].

A subgroup of patients reported significantly more health complaints compared to the remaining patients and controls, which is in accordance with previous studies [13] and [18]. Among these patients, 60% reported a case level score for anxiety and depression. Depression may be an overlooked diagnosis, and regarded as normal reaction to the various burdens these patients experience during treatment [43]. Also, depression, fatigue, and sleep problems may share similar psychological elements [43]. A combination of fatigue severity levels and fatigue interference levels were used to identify fatigue in the participants. Patients reporting strong fatigue interference also reported a high score on anxiety and depression, which is in accordance with recent findings from Traeger et al. [44]. The authors concluded that among cancer patients, elevated depressive symptoms were associated with fatigue interference levels being equal to or greater than fatigue severity levels [44]. Hence, compared with fatigue severity, fatigue interference may be more strongly related to depression among fatigued cancer patients, and may be useful when screening for depression in the context of fatigue [44].

It is conceivable that depression and fatigue is underrated due to, for instance lack of communication between patients and health care professionals [8]. Also, younger women in early menopause may be more vulnerable to symptoms due to oncological treatment [45]. Therefore, it may be essential that the clinicians are aware of signs and symptoms of depression in these women, providing the correct diagnosis, and offering appropriate therapy. This may be of importance in adherence to treatment and the cancer rehabilitation [46]. In this study however, there were no differences in demographic and treatment variables in the two groups of patients. It might be questioned whether this subgroup of patients represent women suffering from comorbidities before the breast cancer diagnosis, which either surfaced to or increased during treatment. If so, it may help to partially explain the predictors for self-reported health complaints found in this study.

Our analyses have some limits. The study is a cross sectional design, which does not identify the causes of the health complaints, whether they are comorbidities or result from breast cancer treatment. All measures were obtained via self-reporting, which is known to cause some uncertainty in the material [47]. Validation of the results in larger studies with other designs is warranted.

Conclusion

Most patients with breast cancer (76%) reported health complaints equal to the controls. Fatigue, anxiety and depression, not oncological treatments, were the significant predictors. For some patients however, the complaints are perceived as more than just a minor inconvenience and should therefore be offered a closer monitoring to prevent a suboptimal adherence to treatment.

Funding

Funds from the Competence Centre for Clinical Research, Haukeland University Hospital, Bergen, Norway, Folke Hermansen Fondation and Inge Steensland Fondation, Stavanger, Norway, supported the work.

Ethics

Regional Committee for Medical Research Ethics (REK–Nord No. 2011/2161) and The Norwegian Social Science Data Services approved the study, and written consent was obtained.

Conflict of interest statement

The authors declare no commercial or financial conflict of interest.

Acknowledgment

Thanks to Sissel Vevle and Eli Bøhme for Collection of patient data.

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Footnotes

a Department of Breast and Endocrine Surgery, Haukeland University Hospital, Bergen, Norway

b Research Department, Stavanger University Hospital, Stavanger, Norway

c Department of Mathematics and Natural Science, University of Stavanger, Stavanger, Norway

d Department of Sport and Physical Activity, Bergen University College, Bergen, Norway

e Uni Research Health, Bergen, Norway

f Department of Surgery, Stavanger University Hospital, Stavanger, Norway

g Department of Clinical Science, University of Bergen, Bergen, Norway

h Department of Medicine, Haukeland University Hospital, Bergen, Norway

i Department of Clinical Medicine, University of Bergen, Bergen, Norway

Corresponding author. Department of Breast and Endocrine Surgery, Haukeland University Hospital, Bergen, N-5021, Norway. Tel.: +47 412 28 693.


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