CC BY
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UCD: 618.19-006.6-089 616.89-008.454
DOI: 10.24411/1995-5871-2020-10128
THE PREVALENCE OF ANXIETY AMONG ADVANCED BREAST CANCER PATIENTS: A SYSTEMATIC REVIEW AND META-ANALYSIS
n I. Karibayeva, 2 B.Turdaliyeva, 3 Nor Zuraida Zainal, 4 F. Bagiyarova
1 2 Kazakh medical university of continuing education, Almaty 3 University of Malaya, Kuala Lumpur, Malaysia 4 S.D. Asfendiyarov Kazakh National medical university, Almaty
SUMMARY
Background. Anxiety in patients with metastatic or recurrent breast cancer is a common psychological comorbidity. This study aims to systematically review the current literature on observational studies with data on the prevalence of anxiety in metastatic and recurrent breast cancer patients, examine the pooled mean prevalence of anxiety and potential sources of heterogeneity.
Methods. An extensive systematic review of PubMed, Web of Science, ScienceDirect, Google Scholar, and Open Grey databases, and following hand-search of the reference list of the included studies was performed.
Results. We identified 16 eligible studies that assessed 1284 patients on the presence of anxiety using structured interviews and two self-report inventories. In total, 371 patients met the criteria for anxiety. According to the random-effects model, the pooled mean prevalence of anxiety was 29.93% (95% CI [23.22; 37.09]; I2= 86%). Studies that reported the prevalence of anxiety in the last fifteen years had the same rate as the studies that were published in the fifteen years before that.
Limitations. Only studies in English were included; no studies from African and SouthEast Asia regions met the criteria; we did not have enough data on the time between diagnosis of breast cancer to the time of the anxiety evaluation; the heterogeneity of the included studies was high. Conclusions. Around one-third of patients with advanced breast cancer are diagnosed with anxiety. Breast cancer patients' high psychological needs have to be recognized and met not only at primary diagnosis but also at recurrence and progression of the disease.
Key words: Breast cancer, anxiety, metastatic, recurrent, systematic review.
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Background. As cancer, regardless of its localization, is a chronic disease that requires constant monitoring and complex treatment, and even then can significantly limit the longevity of a person, there is a certain amount of fear and concern about getting cancer in the general population [1]. Fear of being diagnosed with cancer is one of the main reasons why people delay seeking medical help in time [2]. Understandably, patients with cancer experience a high psychological burden as they have to accept their diagnosis, prognosis and prepare themselves for the treatment strategy, and deal with the change in their normal life [3]. Often the emotional experiences of patients about their cancer
diagnosis include anxiety, confusion, depression, and stress, and some studies show that patients who experience psychological distress have a higher rate of cancer related mortality [4]. Because breast cancer is one of the most prevalent oncological diseases affecting women [5], and women are more likely to have higher levels of psychological symptoms [6], a huge number of studies have been devoted to investigating the psychological needs of breast cancer patients and long-term survivors, and factors associated with them.
According to a systematic review of the descriptive studies that assessed depression among Iranian breast cancer patients, the prevalence of severe and very severe
k indira.karibayeva@gmail.com
depression varied from 10% to 69.4% [7]. Significant variation in depression prevalence among breast cancer patients was also shown in a study that combined results of 72 nonintervention studies, where the depression prevalence ranged from 3% to 95.9% [8]. A study that reviewed 27 articles with the assessment of the anxiety prevalence among breast cancer patients also found that the presence of anxiety of any degree stretched from 4.1% to 97.5% [9]. Those variations make the investigation of the impact of the psychological experiences on the quality of life and overall survival of the patients crucial, as some studies show that underdiagnosed depression and anxiety can reduce the quality of life and cause higher economical loss [10]. In 2013, a review of the literature showed that among long-term breast cancer survivors the depression prevalence varied from 1% to 56% [11]. Breast cancer survivors regardless of the time since diagnosis experience high levels of anxiety and unmet psychological care needs [12]. A study among long-term cancer survivors showed that less than 50% of the survivors received psycho-social care after diagnosis [13]
We have yet to understand the patterns of anxiety duration and severity among breast cancer patients, and its impact on the quality of life, treatment efficacy, and overall survival of the patients. Important questions that arise are: how effective is the regular screening for psychological needs; what approach for regular screening should be implemented; does the prevalence of psychological disorders vary in recurrent and metastatic breast cancer patients versus non-advanced breast cancer patients.
To the authors' best knowledge, a systematic review of the articles that assessed the prevalence of anxiety among metastatic and recurrent breast cancer patients has not been published. It is important to determine, whether advanced breast cancer patients experience a high psychological burden, and whether special policies should be implemented to address their unmet needs.
This study aims to systematically review the current literature on observational studies with data on the prevalence of anxiety in metastatic and recurrent breast cancer patients, examine the pooled mean prevalence of anxiety and potential sources of heterogeneity.
Methods. The study protocol is registered with the PROSPERO International prospective register of systematic reviews (ID: CRD42020153960).
Search strategy. The PROSPERO database was searched to identify the registration of studies that assessed the prevalence of anxiety among metastatic and recurrent breast cancer patients, and similar studies were not found. Therefore, for this review, PubMed, Web of Science, ScienceDirect, Google Scholar, and Open Grey databases were searched from January 1990 till May 2020. The full search strategy of the databases is presented in supplemental materials. After the initial selection of the studies from the database search, we performed a hand search of the literature based on the list of references of the selected articles from the database search.
Eligibility criteria. In this review, we used methods from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The inclusion criteria for the studies: 1) included adults (aged >18); 2) patients had a primary diagnosis of metastatic (stage IV) or recurrent (local, regional, or distant) breast cancer; 3) reported either proportion or number of patients with anxiety using standard evaluation methods; 4) were observational; 5) published in English from January 1990 to May 2020. The exclusion criteria: 1) publications that lacked required information; 2) publications that duplicated previously reported study results; 3) had a high risk of bias; 4) focused specifically on younger or older patient groups;
Selection of studies and data extraction. Following the PRISMA guidelines, the database search, selection of studies based on their inclusion/exclusion criteria, and ^ data extraction were performed by two ^ independent researchers (IK and FB) [14]. Up to two contacts via email were made to authors to obtain missing data. The required ¡g information list was created and approved by ^ all authors, and included: first author, year, ^ country, study design, sampling, number of a eligible and approached patients, number of § responded patients, number of patients with a anxiety, anxiety evaluation scale, mean age, N the proportion of married patients, number of ® patients with depression and risk of bias.
Quality assessment. The nine- ¡5
item Hoy quality assessment checklist for prevalence studies was used to evaluate the risk of bias of the included studies [15]. The risk of bias is low if the study Hoy score is <3. Each researcher evaluated the risk of bias independently for every included article, and disagreements, when present, were resolved through consensus of three authors.
Data analysis. Data analysis was performed using R-studio statistical software. The outcome of interest was the number of patients with anxiety. Data were combined using a forest plot. The pooled average prevalence of anxiety was calculated with Freeman-Tukey double arcsine transformation using random-effects restricted maximum likelihood estimator to handle small sample sizes and extreme proportions. To account for some level of between-study variability and identify potential influential studies for the meta-analysis results we calculated the studentized residuals, performed a leave-one-out analysis, and calculated the pooled mean prevalence of anxiety when the influential studies were removed. To examine whether clinical and sociodemographic factors account for the heterogeneity in the prevalence of anxiety among metastatic and recurrent breast cancer
patients, we performed the univariable metaregression analysis. To further explore the sources of heterogeneity, several subgroup analyses were performed. For the subgroup analysis, because of the different sample sizes, we assumed a common between-study variance component and pooled within-group estimates of between-study variance.
Assessment of risk of bias across studies. To detect the risk of publication bias, we plotted the proportion of patients with anxiety in each included study by the inverse of its standard error, and then by the inverse of the sample size. Visually examined the funnel plots, and performed the Egger's unweighted regression test for funnel plot asymmetry.
Results. The initial search of PubMed, Web of Science, ScienceDirect, Google Scholar, and Open Grey retrieved 2 814 articles. After eliminating duplicates, not relevant articles, systematic reviews, letters to the editor, 94 studies were screened for their eligibility criteria, and thirteen studies met the criteria. The reference search included 421 references listed in the included articles, where three articles met the inclusion criteria. A secondary reference search included 112 articles, but no additional studies were selected (Figure №1).
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Figure №1. The PRISMA flowchart of study selection
Characteristics of included studies. The proportion or number of patients with anxiety was reported in sixteen studies, using three different diagnostic methods, such as structured interview, Beck Anxiety Inventory (BAI), and Hospital Anxiety and Depression Scale (HADS). HADS was the most frequently used anxiety inventory, as it was used in nine studies. Studies were conducted in eight countries, with seven studies taking place in the United Kingdom (UK), and three in Japan. In all included papers the sampling method was consecutive. Twelve studies employed the cross-sectional design, two studies employed the cohort design, one study employed the descriptive design and one study used the prospective design. The sample size ranged from 22 to 211 participants, with a mean sample size of 80 participants. All included articles had a low risk of bias and scored three
or below on the Hoy scale.
1 373 patients were eligible and approached, and 1 284 (93.52%) patients agreed to participate in the prevalence studies. The mean age of participants was 55.35 (range: 47-65). In total, 371 patients met the criteria for anxiety. The lowest prevalence of anxiety of 12% according to the structured interview results was reported among 25 recurrent breast cancer patients in Egypt [16]. The highest prevalence of anxiety of 66% was reported among 44 metastatic breast cancer patients in the UK [17]. In a study by El Missiry and colleagues, the prevalence of anxiety was reported according to the structured interview (DSM-IV) and BAI results, only the number of patients with anxiety according to the structured interview results was included to the present count and meta-analysis of patients with anxiety [16] (Table №1)
Table №1. Demographic characteristics of the included studies
№ First author" Year Country Income level WHO region Hoy score Design Sampling Sample size Pts with anxiety, n (%) Anxiety Scale Age, years mean <SD| Married ii(%) Pts with depression, » (%)
1 Alfano A.C. [35] 2013 Brazil upper-middle Americas 3 cross-sectional consecutive 126 46 (36.5) HADS 51.4 (10,9) 74(58.7) 47 (37.3)
2 DraRomir B 1. 1181 2013 Romania upper-middle European 3 cross-sectional consecutive 62 38 (61.3) BAI 54.4 48(81.8)
3 El Missiry [16) 2011 Egypt lower-middle Eastern Mediterranean 3 cross-sectional consecutive 25 15 (60) interview 47 (9.6) 18(72) 3(12)
4 Fulton C.L. [17J 1997 UK high European 3 cross-sectional consecutive 44 29 (66) HADS 492 36181.8) 22 (50)
5 Fulton C.L 1361 1998 UK high European 3 cohort consecutive 80 31(39) HADS 53.75 64(80) 25(31)
6 Hall A. |37| 1996 UK high European 3 cohort convenience 38 14(36.8) interview 13 (34.2)
7 Hopwood P. a [381 1991 UK high European 3 cross-sectional consecutive 211 37(18.0) HADS 38(18.01)
g Hopwood P. b |39| 1991 UK high European 3 cross-sectional consecutive 81 12 (14.8) interview 16(19.8)
9 Jdm C.F. (40] 2012 Germany high European 3 cross-sectional consecutive 70 23 (32.9) HADS 59.9 22 (31.4)
10 Jenkins P L |411 1991 UK hinh European 3 prospective consecutive 22 6 (27.3) interview 54.1 7(31.8)
]] Okamuni M. [42] 2005 Japan high Western Pacific 3 cross-sectional consecutive 50 6(12) interview 53 42(84) 10 (20)
12 Okamura M. [43] 2000 Japan high Western Pacific 3 cross-sectional consecutive 55 15 (27.3) interview 52 47(86) 17 (30.9)
13 Pinder K..L. [44] 1993 UK high European 3 cross-sectional consecutive 139 27 (19.4) HADS 60.5 98(70.5) 17(12.2)
14 Sarenmalm E.K_ 1451 2007 Sweden high European 3 descriptive consecutive 56 16 (29) HADS 65 35(62,5) 12(21.4)
15 Shin J A. [46J 2016 USA high Americas 3 cross-sectional consecutive 140 40 (28.6) HADS 60.7 (12.08) 83 (59.3) 25(17.9)
16 Uchida M [47] 2011 Japan high Western Pacific 2 cross-sectional randomly selected 85 28 (32.9) HADS 58,6 68(80) 12 (14.1)
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Abbreviations: BAI, Beck Anxiety Inventory; HADS, Hospital Anxiety and Depression Scale; mts, metastasis; n, number; Pts, patients; SD, standard deviation; UK, the United Kingdom; USA, the United States of America; WHO, World Health Organization
Pooled mean prevalence of anxiety. 86%). Test for heterogeneity suggests
Based on the random-effects model, the high heterogeneity in the anxiety
pooled mean prevalence of anxiety was prevalence: Q (df = 15) = 104.59, p-val <
29.93% (95% CI [23.22; 37.09]; I2= 0.0001 (Figure №2).
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Figure №2. Prevalence of anxiety based on the random-effects model among advanced breast
cancer patients
Study Events Total Wei y ht IV, Random, 95% (
Fulton С _ 1997 29 44 5.9% 0.66 [0.50: 0.80]
□ ragomir Б I 2013 38 62 6.3% 0.61 [0.48; 0.73]
Fulton С _ 1998 31 80 6.5% 0.39 [0.28; 0.50]
Hall A. 1996 14 38 5.7% 0.37 [0.22; 0.54]
Alfa no A.C. 2013 46 126 6.9% 0.37 [0.28; 0.46]
Uchida M. 2011 28 85 6.6% 0.33 [0.23; 0 44]
Jehn C.F. 2012 23 70 6.4% 0.33 [0.22; 0 45]
Sarenmalm E.K. 2007 1E 56 6.2% 0.29 [0.17; 0.42]
Shin JA.. 2016 40 140 7.0% 0.29 [0.21. 0.37]
Jenkins P. L. 1991 Б 22 4.8% 0.27 [0.11: 0.50]
Okamura M. 2000 15 55 6.1% 0.27 [0.16; 0.41]
Pinder K.L 1993 27 139 6.9% 0 19 [0.13; 0.27]
Hopwood P. 1991 a 37 211 7.2% 0.18 [0.13; 0.23]
Hopwood P. 1991 b 12 81 6.5% 0 15 [0.08: 0.24]
El Missiry 2011 3 25 5.0% 0.12 [0.03; 0.31]
Okamura M. 2005 6 50 6.0% 0 12 [0.05: 0.24]
Total (95% CI) 1284 100.0% 0.30 [0.23; 0.37]
Heterogeneity: Tau; = 0.0190; Ch¡; = 104.59, df = 15 [P < 0.01); I =36%
IV, Random, 95% CI
T
T
I I r
0 0.2 0.4 0.6 0.8 1 Proportion of patients with anxiety
(Abbreviations: CI, confidence interval; I2, percentage of variability in the effect sizes which is not caused by sampling error; Tau2, between-study variance in the meta-analysis; Chi2, (Q-statistic) difference between the observed effect sizes and the fixed-effect model estimate of the effect size).
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According to the analysis that identifies the most influential studies, studentized residuals that are larger than "2" were identified in two studies with the highest prevalence of anxiety of more than 60% [17] [18]. When those studies were removed, the pooled mean prevalence of anxiety based on the random-effects model was lower at 25.72% (95% CI [20.89; 30.84].
Assessment of risk of bias across studies. On the funnel plot with the standard error on the y-axis and the proportion of patients with anxiety on the x-axis, two studies that we previously identified as the most influential studies were further away from the pooled mean prevalence line. Several studies were located outside of the 95% CI limit lines, which is indicative of the high heterogeneity of the included studies. Visually we did not find
clear evidence of the funnel plot asymmetry. To examine, if the method of funnel plot construction can induce the asymmetry, we plotted the sample size of the included studies on the y-axis, and the proportion of patients with anxiety on the x-axis. The second plot also did not have clear evidence of the asymmetry. The Egger's unweighted regression tests for both plots were not statistically significant, and returned z = 0.29, p = 0.77 for the first plot, and z = -0.96, p = 0.34 for the second plot. Our findings suggest that the risk of publication bias across included studies was low.
Meta-regression finding. According to the meta-regression findings, the publication year, mean age of participants, being married, being depressed and sample size did not significantly account for the heterogeneity in the effect sizes between studies (Table №2).
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Table №2. Meta-regression model results
Coefficient Estimate Standard error z-value p-value
Publication year (year) 0.84 0.004 0.005 0.92 0.36
Mean age (years) 0.27 -0.005 0.01 -0.52 0.61
Married patients (%) 0.37 0.004 0.006 0.60 0.55
Depressed patients (%) 3.02 0.005 0.003 1.74 0.08
Sample size (n) 0.93 -0.0008 0.0008 -0.96 0.34
Subgroup analysis of studies that reported the number of patients with anxiety. Subgroup analysis based on the years that the studies were conducted, showed that the pooled prevalence of anxiety in the last fifteen years was almost the same as in
the previous fifteen years at 30.35% (95% CI [20.07; 41.68], I2=83%, p<0.01) and 29.55% (95% CI [19.30; 40.91], I2=87%, p<0.01) respectively (Figure №3). The test for subgroup differences was not statistically significant, p=0.92.
Figure №3. Subgroup analysis of the depression prevalence based on the random-effects model among advanced breast cancer patients by the years that the studies were conducted
Study Events Total Weight IV, Random, 95% (
Fulton С . 1997 29 44 6.9% 0.66 [0.50. 0.80]
Dragomir El 2013 38 62 6.3% 0.61 [0.48: 0.73]
Fulton С . 1998 31 80 6.5% 0.39 [0.28; 0.50]
Hall A. 1996 14 38 5.7% 0.37 [0.22; 0.54]
Alfano A.C. 2013 46 126 6.9% 0.37 [0.28: 0.46]
Uchida M. 2011 28 85 6.6% 0.33 [0.23: 0.44]
Jehn C.F. 2012 23 70 6.4% 0.33 [0.22: 0.45]
Sarenmalm E.K. 2007 16 56 6.2% 0.29 [0.17: 0.42]
Shin J.A. 2016 40 140 7.0% 0.29 [0.21: 0.37]
Jenkins P. L. 1991 6 22 4.8% 0.27 [0 11. 0.60]
Okamura M. 2000 15 55 6.1% 0.27 [0.16: 0.41]
Pinder K.L. 1993 27 139 6.9% 0 19 [0.13; 0.27]
Hopwood P. 1991 a 37 211 7.2% 0.18 [0.13; 0.23]
Hopwood P. 1991 b 12 81 6.5% 0.15 [0.08: 0.24]
El Missiry 2011 3 25 5.0% 0.12 [0.03; 0.31]
Okamura M. 2005 6 50 6.0% 0 12 [0.05: 0.24]
Total (95% CI) 1284 100.0% 0.30 [0.23; 0.37]
Heterogeneity: Tau' = 0.0190; Chi2 = 104.59, df - 15 [P 0.01); I =36%
IV, Random, 951i CI
T
T
-1-r
0.2 0.4 0.6 0.8 1 Proportion of patients with anxiety
(Abbreviations: Chi2, (Q-statistic) difference between the observed effect sizes and the fixed-effect model estimate of the effect size; CI, confidence interval; P, percentage of variability in the effect sizes which is not caused by sampling error; Tau2, between-study variance in the meta-analysis).
Subgroup analysis based on the anxiety evaluation method showed that the pooled prevalence of anxiety among advanced breast cancer patients was higher when reported
according to the HADS results at 32.15% (95% CI [24.41; 40.40], I2=85%, p<0.01) (k=9) compared to the pooled prevalence of anxiety reported according to the interview
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results at 20.75% (95% CI [11.98; 31.03], test for subgroup differences was statistically I2=59%, p<0.03) (k=6) (Figure №4). The significant, p=0.01.
Figure 4. Subgroup analysis of the depression prevalence based on the random-effects model among advanced breast cancer patients by the anxiety evaluation method
(Abbreviations: BAI, Beck Anxiety Inventory; Chi2, (Q-statistic) difference between the observed effect sizes and the fixed-effect model estimate of the effect size; CI, confidence interval; HADS, Hospital Anxiety and Depression scale; I2, percentage of variability in the effect sizes which is not caused by sampling error; Tau2, between-study variance in the meta-analysis).
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Sub-group analyses based on the cancer type showed that the combined prevalence of anxiety was higher in studies that focused only on metastatic breast cancer patients, and lower in studies with recurrent (local, regional or distant) breast cancer patients at 35.51% (95% CI [25.23; 46.50], I2=92%, p<0.01) and 23.47% (95% CI [12.60; 36.31], I2=54%, p=0.06). The pooled prevalence of anxiety in mixed studies that focused on recurrent and metastatic breast cancer patients was closer to the pooled mean prevalence of anxiety at 25.73% (95% CI [09.29; 46.72]; I2=80%, p=0.02). The test for subgroup differences
was not statistically significant, p=0.33.
Subgroup analysis based on the World Health Organization (WHO) regions showed that the pooled prevalence of anxiety was higher in the European and in the Americas regions at 33.07% (95% CI [23.45; 43.42], I2=90%, p<0.01) and 32.46% (95% CI [13.69; 54.71], I2=47%, p=0.17) respectively. The lowest prevalence of anxiety was detected in the Eastern Mediterranean region at 12% (95% CI [0; 45.00]). Unfortunately, we only had one study from the Eastern Mediterranean region (Figure №5). The test for subgroup differences was not statistically significant, p=0.53.
Figure №5. Subgroup analysis of the depression prevalence based on the random-effects model among advanced breast cancer patients by WHO regions
Study or
Subgroup Events
'WHO region' = European
Fulton C.L. 1997 29
Dragomir B.I. 2013 38
Fulton C.L. 1998 31
Hall A. 1996 14
JehnC.F. 2012 23
Sarenmalm E.K. 2007 16
Jenkins P. L. 1991 6
Pinder K.L. 1993 27
Hopwood P. 1991 a 37
Hopwood P. 1991 b 12 Total (95% CI)
Heterogeneity: Tau2 = 0.0244; Chi2
Total Weight IV, Random, 95% CI
44 5.9%
62 6.3%
80 6.5% 38 5.8% 70 6.4% 56 6.2% 22 5.0%
139 6.8%
211 7.0%
81 6.5% 803 62.4%
: 88.34, df = 9 (P
0.66 [0.51; 0.79] 0.61 [0.49; 0.73] 0.39 [0.28; 0.50] 0.37 [0.22; 0.53] 0.33 [0.22; 0.44] 0.29 [0.17; 0.41] 0.27 [0.10; 0.48] 0.19 [0.13; 0.26] 0.18 [0.13; 0.23] 0.15 [0.08; 0.23] 0.33 [0.23; 0.43] : 0.01); I2 = 90%
"WHO region' = Americas
AlfanoA.C. 2013 46 126 6.8% 0.37 [0.28; 0.45]
Shin J.A. 2016 40 140 6.8% 0.29 [0.21; 0.36]
Total (95% CI) 266 1 3.6% 0.32 [0.14; 0.55]
Heterogeneity: Tau2 = 0.0244; Chi2 = 1.89, df = 1 (P = 0.17); I2 = 47%
'WHO region' = Western Pacific Uchida M. 2011 28 85
Okamura M. 2000 15 55
Okamura M. 2005 6 50
Total (95% CI) 190
6.1%
18.8%
0.33 [0.23; 0.43] 0.27 [0.16; 0.40] 0.12 [0.04; 0.23]
0.24 [0.09; 0.42]
Heterogeneity: Tai/ = 0.0244; Chf = 8.02, df = 2 (P = 0.02); f = 75%
'WHO region' = Eastern Mediterranean El Missiry 2011 3 25 5.2%
Total (95% CI) 25 5.2%
Heterogeneity: not applicable
0.12 [0.02; 0.28]
0.12 [0.00; 0.45]
Total (95% CI) 1284 100.0% 0.30 [0.23; 0.38]
Heterogeneity: Tau2 = 0.0244; Chi2 = 104.59, df = 15 (P < 0.01); I2 = 86% Residual heterogeneity: Tau2 = NA; Chi2 = 98.24, df = 12 (P < 0.01); I2 = 8£
IV, Random, 95% CI
0.4 0.6 Proportion
Subgroup analysis based on the income level of the country where a study was conducted, showed that the pooled prevalence of anxiety in upper-middle-income countries was the highest at 48.20% (95% CI [28.69; 68.00]; I2=90%; p<0.01). The test for subgroup differences was not statistically significant, p=0.08.
The graphical representation of the subgroup analysis results is presented in the supplemental materials.
Discussion. The prevalence of anxiety in advanced breast cancer patients varies from 12% to 66% according to the papers that were included in the present analysis. Based on the results of our meta-analysis, the global prevalence of anxiety among 1284 advanced breast cancer patients was 29.93% (95% CI [23.22; 37.09]). According to the meta-analysis of anxiety prevalence among breast cancer patients which included twenty-seven articles, the range of anxiety prevalence was wider at 4.1% to 97.5%, and pooled mean prevalence of anxiety was also higher at 41.9% (95% CI [30.7; 53.2]) [9]. This difference
could be attributable to the specific focus of the present analysis on the advanced stage, methodological variations, and a smaller number of studies analyzed. A previous study that investigated the relationship between anxiety and depression after diagnosis and cancer stage showed that advanced stage did not predict higher levels of anxiety among breast cancer patients [19].
Some authors argue that the prevalence of anxiety in breast cancer patients has increased in recent years [9]. In the present meta-analysis, this factor was not analyzed, as only studies that were published up to 2016 met the eligibility criteria. Studies that reported the prevalence of anxiety in the last fifteen years group (2005 -2020) had the same rate as the studies that were published in the fifteen years before that (1990 - 2014) at 30.35% (95% CI [20.07; 41.68]) and 29.55% (95% CI [19.30; 40.91]) respectively. Exploring whether the anxiety rate of breast patients has increased in the last five years, and if it could be explained with the wider range of therapeutic options presented to a patient is an interesting topic for further research.
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The methodology of anxiety diagnosis has been a significant factor that could influence the number of patients with anxiety. Some studies show that the anxiety diagnosis rate was higher when self-assessment inventories were used compared to the structured interview results [20], and the results of the present meta-analysis confirm previous findings. The prevalence of anxiety reported according to the results of the structured interview was significantly lower than the prevalence rate reported with the HADS inventory at 20.75% (95% CI [11.98; 31.03]) and 32.15% (95% CI [24.41; 40.40]) respectively. Generally, most of the self-report scales were reported to be designed as a screening instrument, but not as a diagnostic tool [21] [22] [23] [24]. Nevertheless, some authors argue that the combined use of self-report inventories and structured interview is the best way to identify patients with psychological needs [20]. Another topic for further research could be to look at the influence of underdiagnosed anxiety on the survival rate of breast cancer patients.
Among clinical factors that were explored as the potential sources of heterogeneity, subgroup difference for cancer type was not statistically significant, although the metastatic group had a higher prevalence of anxiety than the recurrent group at 35.51% (95% CI [25.23; 46.50]) and 23.47% (95% CI [12.60; 36.31]) respectively. Further research is needed to explore whether the anxiety rate of the de novo metastatic breast cancer patients is different from the patients with recurrent breast cancer and whether those patients require different approaches to manage their high psychological needs. Meta-regression analysis based on the depression prevalence among breast cancer patients was also not statistically significant. Nevertheless, the correlation between the number of depressed patients and the number of patients with anxiety was positive.
Among sociodemographic factors that were explored as the potential sources of heterogeneity, we found that the European and
the Americas region had a higher prevalence of anxiety (33.07% (95% CI [23.45; 43.42]) and 32.46% (95% CI [13.69; 54.71]) respectively) than the Eastern Mediterranean region at 12% (95% CI [0; 45.00]). Previously reported studies show that patients with breast cancer in the Eastern Mediterranean region have a higher prevalence of psychological comorbidities that are attributed to the younger age of patients, and a later stage of the disease at diagnosis [8].
The limitations of the present systematic review and meta-analysis are the following: 1) We only included published studies in English, and acknowledge that we could not eliminate the publication bias; 2) No studies from African and South-East Asia regions met the eligibility criteria of the present metaanalysis; 3) We did not have enough data on the time between diagnosis of breast cancer to the time of the anxiety evaluation. To make results more homogenous, we excluded studies that reported anxiety prevalence among long term survivors with metastatic breast cancer [25]; 4) The heterogeneity of the included studies was high, although we excluded studies that: a) focused only on geriatric or young advanced breast cancer patients [26] [27] [28] [29]; b) had stage III and stage IV breast cancer patients, if they did not define their stage III patients as recurrent [30] [31] [32] [33] or reported anxiety before recurrence [34].
Clinical implications of our findings: breast cancer patients' high psychological needs have to be recognized and met not only at primary diagnosis but also at recurrence and progression of the disease.
Conclusion. Our findings show that every third patient with metastatic and recurrent breast cancer is at risk of having anxiety. Healthcare providers must implement special policies to address the timely diagnosis of the presence of psychological disorders, initiation, and maintenance of the adequate psycho-social care and support of the breast cancer patients throughout the entire course of the treatment and beyond during their survivorsh
REFERENCES
1. Vrinten C., McGregor L.M., Heinrich M., von Wagner C., Waller J., Wardle J., et al. What do people fear about cancer? A systematic review and meta-synthesis of cancer fears in the general population. Psychooncology. 2017;26:1070-9. doi:10.1002/pon.4287.
2. Cipora E., Konieczny M., Czerw A., Mikos M., Budzik M.P., Deptala A, et al. Causes of delays in breast cancer diagnosis in Poland. Pol Merkur Lekarski. 2019;47:85-90.
3. Hack T.F., Degner L.F. Coping responses following breast cancer diagnosis predict psychological adjustment three years later. Psychooncology. 2004;13:235-47. doi:10.1002/ pon.739.
4. Lu D., Andrae B., Valdimarsdottir U., Sundstrom K., Fall K., Sparen P., et al. Psychological distress is associated with cancer-specific mortality among patients with cervical cancer. Cancer Res. 2019.
5. Bray F., Ferlay J., Soerjomataram I., Siegel R.L., Torre L.A., Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394-424.
6. Ahmad S, Bangash H, Khan SA. Emotional intelligence and gender differences. Sarhad J Agric. 2009;25:127-30.
7. Jafari A., Goudarzian A.H., Bagheri Nesami M. Depression in Women with Breast Cancer: A Systematic Review of Cross-Sectional Studies in Iran. Asian Pac J Cancer Prev. 2018;19:1-7.
8. Pilevarzadeh M., Amirshahi M., Afsargharehbagh R., Rafiemanesh H., Hashemi S.M., Balouchi A. Global prevalence of depression among breast cancer patients: a systematic review and meta-analysis. Breast Cancer Res Treat. 2019;176:519-33. doi:10.1007/s10549-019-05271-3.
9. Hashemi S.M., Rafiemanesh H., Aghamohammadi T., Badakhsh M., Amirshahi M., Sari M., et al. Prevalence of anxiety among breast cancer patients: a systematic review and meta-analysis. Breast Cancer. 2019;:1-13.
10. Williams S.Z., Chung G.S., Muennig P.A. Undiagnosed depression: A community diagnosis. SSM - Popul Heal. 2017;3:633-8. doi:10.1016/j.ssmph.2017.07.012.
11. Zainal N.Z., Nik-Jaafar N.R., Baharudin A., Sabki Z.A., Ng C.G. Prevalence of depression in breast cancer survivors: a systematic review of observational studies. Asian Pacific J Cancer Prev. 2013;14:2649-56.
12. Hodgkinson K., Butow P., Hunt G.E., Pendlebury S., Hobbs K.M., Wain G. Breast cancer survivors' supportive care needs 2-10 years after diagnosis. Support Care Cancer. 2007;15:515-23. doi:10.1007/s00520-006-0170-2.
13. Forsythe L.P., Kent E.E., Weaver K.E., Buchanan N., Hawkins N.A., Rodriguez J.L., et al. Receipt of psychosocial care among cancer survivors in the United States. J Clin Oncol. ^ 2013;31:1961-9. doi:10.1200/JCO.2012.46.2101.
14. Liberati A., Altman D.G., Tetzlaff J., Mulrow C., G0tzsche P.C., Ioannidis JPA, et > al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009;339:b2700. « doi:10.1136/bmj.b2700. |
15. Hoy D., Brooks P., Woolf A., Blyth F., March L., Bain C., et al. Assessing risk of bias in prevalence studies: modification of an existing tool and evidence of interrater agreement. J a Clin Epidemiol. 2012;65:934-9. g
16. El Missiry A. Psychiatric Morbidity, Pattern of Coping among sample of Egyptian Women in Early Versus Recurrent Stage of Cancer Breast. Arab J Psychiatry. 2011;Vol. 22:Page
a
a
(36-44). |
17. Fulton C.L. The physical and psychological symptoms experienced by patients with
s
a
metastatic breast cancer before death. Eur J Cancer Care (Engl). 1997;6:262-6. doi:10.1046/ j.1365-2354.1997.00057.x.
18. Dragomir B-I, Fodoreanu L. Correlations between state anxiety and quality of life in metastatic breast cancer patients. Medical-Surgical J. 2013;117:610-5.
19. Vodermaier A., Linden W., MacKenzie R., Greig D., Marshall C. Disease stage predicts post-diagnosis anxiety and depression only in some types of cancer. Br J Cancer. 2011;105:1814-7. doi:10.1038/bjc.2011.503.
20. Hopwood C.J., Morey L.C., Edelen M.O., Shea M.T., Grilo C.M., Sanislow C.A., et al. A comparison of interview and self-report methods for the assessment of borderline personality disorder criteria. Psychological Assessment. 2008;20:81-5.
21. Mitchell A.J., Meader N., Symonds P. Diagnostic validity of the Hospital Anxiety and Depression Scale (HADS) in cancer and palliative settings: a meta-analysis. J Affect Disord. 2010;126:335-48.
22. Wang G., Hsu S., Feng A., Chiu C., Shen J., Lin Y., et al. The HADS and the DT for screening psychosocial distress of cancer patients in Taiwan. Psycho-oncology. 2011;20:639-46.
23. Warmenhoven F., van Rijswijk E., Engels Y., Kan C., Prins J., Van Weel C., et al. The Beck Depression Inventory (BDI-II) and a single screening question as screening tools for depressive disorder in Dutch advanced cancer patients. Support care cancer. 2012;20:319-24.
24. Hann D., Winter K., Jacobsen P. Measurement of depressive symptoms in cancer patients: evaluation of the Center for Epidemiological Studies Depression Scale (CES-D). J Psychosom Res. 1999;46:437-43.
25. Meisel J.L., Domchek S.M., Vonderheide R.H., Giobbie-Hurder A., Lin N.U., Winer EP, et al. Quality of Life in Long-Term Survivors of Metastatic Breast Cancer. Clin Breast Cancer. 2012;12:119-26. doi:https://doi.org/10.1016/j.clbc.2012.01.010.
26. Park EM., Gelber S., Rosenberg S.M., Seah DSE, Schapira L., Come S.E., et al. Anxiety and Depression in Young Women With Metastatic Breast Cancer: A Cross-Sectional Study. Psychosomatics. 2018;59:251-8. doi:https://doi.org/10.1016/j.psym.2018.01.007.
27. Mehmood T. Evaluation of depression and anxiety in young women with metastatic breast cancer. The Breast. 2018;41:S28-9.
28. Hamaker M.E., Seynaeve C., Wymenga ANM, van Tinteren H., Nortier JWR, Maartense E., et al. Baseline comprehensive geriatric assessment is associated with toxicity and survival in elderly metastatic breast cancer patients receiving single-agent chemotherapy: Results from the OMEGA study of the Dutch Breast Cancer Trialists' Group. The Breast. 2014;23:81-7. doi:https://doi.org/10.1016/j.breast.2013.11.004.
29. Aaldriks A.A., Giltay E.J., Le Cessie S., van der Geest LGM, Portielje JEA, Tanis B.C., et al. Prognostic value of geriatric assessment in older patients with advanced breast cancer receiving chemotherapy. The Breast. 2013;22:753-60.
it 30. Hamash K.I., Umberger W., Aktas A., Walsh D., Cheruvu V.K. The Effect of the Pain
Symptom Cluster on Performance in Women Diagnosed with Advanced Breast Cancer: The Mediating Role of the Psychoneurological Symptom Cluster. Pain Manag Nurs. 2018;19:627-^ 36. doi:https://doi.org/10.1016/j.pmn.2018.05.002.
§ 31. Au A., Lam W., Tsang J., Yau T., Soong I., Yeo W., et al. Supportive care needs in Hong
^ Kong Chinese women confronting advanced breast cancer. Psychooncology. 2013;22:1144-51.
32. Valderrama Rios MC, Sanchez Pedraza R., Rios MCV, Pedraza R.S. Anxiety and
depression disorders in relation to the quality of life of breast cancer patients with locally ! advanced or disseminated stage. Rev Colomb Psiquiatr (English ed). 2018;47:211-20. doi:https://doi.org/10.1016/j.rcpeng.2018.10.001.
33. Akechi T., Nakano T., Okamura H., Ueda S., Akizuki N., Nakanishi T., et al. Association Between Self-Reported Sleep Disturbance and Other Symptoms in Patients with Advanced Cancer. Support CARE CANCER. 2018;14:549-55. doi:10.1007/s00520-016-3207-1.
34. Thornton L.M., Andersen B.L., Carson W.E. 3rd. Immune, endocrine, and behavioral precursors to breast cancer recurrence: a case-control analysis. Cancer Immunol Immunother. 2008;57:1471-81.
35. Alfano ACC, Paiva C.E., Rugno F.C., da Silva R.H., Paiva BSR. Biologically based therapies are commonly self-prescribed by Brazilian women for the treatment of advanced breast cancer or its symptoms. Support Care Cancer. 2014;22:1303-11. doi:10.1007/s00520-013-2087-x.
36. Fulton C. The prevalence and detection of psychiatric morbidity in patients with metastatic breast cancer. Eur J Cancer Care (Engl). 1998;7:232-9.
37. Hall A., Fallowfield LJ, A'Hern RP. When Breast Cancer Recurs: A 3-Year Prospective Study of Psychological Morbidity. Breast J. 1996;2:197-203. doi:10.1111/j.1524-4741.1996. tb00095.x.
38. Hopwood P., Howell A., Maguire P. Psychiatric morbidity in patients with advanced cancer of the breast - prevalence measured by 2 self-rating questionnaires. Br J Cancer. 1991;64:349-52.
39. Hopwood P., Howell A., Maguire P. Screening for psychiatric morbidity in patients with advanced breast cancer: validation of two self-report questionnaires. Br J Cancer. 1991;64:353-6.
40. Jehn C.F., Flath B., Strux A., Krebs M., Possinger K., Pezzutto A., et al. Influence of age, performance status, cancer activity, and IL-6 on anxiety and depression in patients with metastatic breast cancer. Breast Cancer Res Treat. 2012;136:789-94. doi:10.1007/s10549-012-2311-2.
41. Jenkins P.L., May V.E., Hughes L.E. Psychological morbidity associated with local recurrence of breast cancer. Int J Psychiatry Med. 1991;21:149-55.
42. Okamura M., Yamawaki S., Akechi T., Taniguchi K., Uchitomi Y. Psychiatric disorders following first breast cancer recurrence: Prevalence, associated factors and relationship to quality of life. Jpn J Clin Oncol. 2005;35:302-9.
43. Okamura H., Watanabe T., Narabayashi M., Katsumata N., Ando M., Adachi I., et al. Psychological distress following first recurrence of disease in patients with breast cancer: prevalence and risk factors. Breast Cancer Res Treat. 2000;61:131-7.
44. Pinder K.L., Ramirez A.J., Black M.E., Richards M.A., Gregory W.M., Rubens R.D. Psychiatric disorder in patients with advanced breast cancer: prevalence and associated factors. Eur J Cancer. 1993;29A:524-7. doi:10.1016/s0959-8049(05)80144-3.
45. Kenne Sarenmalm E., Ohlen J., Jonsson T., Gaston-Johansson F. Coping with Recurrent Breast Cancer: Predictors of Distressing Symptoms and Health-Related Quality of Life. J Pain Symptom Manage. 2007; 34:24-39. doi:https://doi.org/10.1016/j.jpainsymman.2006.10.017.
46. Shin J.A., El-Jawahri A., Parkes A., Schleicher S.M., Knight H.P., Temel J.S. Quality of life, mood, and prognostic understanding in patients with metastatic breast cancer. J Palliat Med. 2016;19:863-9. §
47. Uchida M., Akechi T., Okuyama T., Sagawa R., Nakaguchi T., Endo C., et al. Patients' > Supportive Care Needs and Psychological Distress in Advanced Breast Cancer Patients in
Japan. Jpn J Clin Oncol. 2011;41:530-6. 1
©
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Indira Karibayeva https://orcid.org/0000-0003-1796-2604 Botagoz Turdaliyeva https://orcid.org/0000-0001-9884-0777
Nor Zuraida Zainal https://orcid.org/0000-0002-3519-711X «
Fatima Bagiyarova https://orcid.org/0000-0003-0000-1321 s
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List of abbreviations (used in the text)
BAI - Beck Anxiety Inventory
HADS - Hospital Anxiety and Depression Scale
PRISMA - Preferred Reporting Items for Systematic Reviews and Meta-Analyses
UK - United Kingdom
WHO - World Health Organization
CYT БЕЗ1 КАТЕРЛ11С1Г1 АУРУЫ БАР НАУКАСТАР АРАСЫНДА МАЗАСЫЗДЫКТЫЦ ТАРАЛУЫ: ЖУЙЕЛ1 ШОЛУ ЖЭНЕ МЕТА-АНАЛИЗ
n И. Карибаева, 2Б.Турдалиева, 3 Нор Зураида Зайнал, 4 Ф. Багиярова
1 2 ^азак медициналык Yздiксiз бiлiм беру университет^ Алматы к-сы 3 Малай университет^ Куала-Лумпур, Малайзия 4 С.Д. Асфендияров атындагы ^азак ¥лттык медициналык университетi, Алматы к-сы
ТУЙ1НД1
Юркпе. Метастатикалы; немесе кайта пайда болган сYт безшщ катерлi iсiгi бар наукастардагы мазасыздык - бул жалпы психологиялык iлеспе ауру. Бул зерттеудщ максаты - метастатикалык жэне кайта пайда болган сYт безшщ катерлi iсiгi бар наукастардагы мазасыздыктыц таралуы туралы мэлiметтерi бар обсервациялык зерттеулердi жYЙелi тYPде карастыру, мазасыздыктыц жинакталган орташа таралуы мен потенциалды гетерогендшпн зерттеу.
Эд1стер. PubMed, Web of Science, ScienceDirect, Google Scholar жэне Open Grey дереккорларына кец жYЙелi шолу жасап, бiрiншi кезекте тацдалып алынган зерттеулердщ сiлтiмiлерiне кайта шолу жасау.
Нэтижелер. ¥сынылып отыргын жYЙелi карастыруга бiз курастырылган сухбат пен ею тYрлi сауалнаманы колдана отырып 1284 пациентте мазасыздыкты зерттеген 16 лайьщты зерттеудi костык. Барлыгы 371 наукас мазасыздык критерийлерiне сай бол-ды. Кездейсок эффекттер моделiне сэйкес мазасыздыктыц жинакталган орташа таралуы 29.93% курады (95% CI [23.22; 37.09]; I2 = 86%). Соцгы он бес жылда баяндалган мазасыздыктыц таралуы осыдан он бес жыл бурын шыккан зерттеулердегi мазасыздыктыц таралуына тец келдi.
Шектеулер. Тек агылшын тiлiндегi зерттеулер енгiзiлдi; Африка жэне Ощуспк-Шыгыс Азия аймактарында жYргiзiлген зерттеулер зерттеуге косу критерийлерге сэйкес келмедц бiзде CYт безi катерлi iсiгiнiц диагнозы мен мазасыздыкты багалау уакытына дейiнгi уакыт туралы мэлiметтер жеткiлiксiз болды; енгiзiлген зерттеулердiц эртектшгт ^ жогары болды.
^ ^орытынды. СYт безi катерлi iсiгi бар наукастардыц шамамен Yштен бiр белшнде
^ мазасыздык бар. СYт безi катерлi iсiгi бар наукастардыц жогары психологиялык ^ кажеттiлiктерiн алгашкы диагноз кою кезшде гана емес, сонымен катар аурудыц <а кайталануы мен ершуi кезiнде де мойындау жэне канагаттандыру кажет.
КЫт свздер: сут безШц vpmepni iciei, мазасыздыц, метастатикалыц,
цаиталанатын, жуиетк шолу.
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йз
РАСПРОСТРАНЕННОСТЬ ТРЕВОГИ СРЕДИ ПАЦИЕНТОВ С РАСПРОСТРАНЕННЫМ РАКОМ МОЛОЧНОЙ ЖЕЛЕЗЫ: СИСТЕМАТИЧЕСКИЙ ОБЗОР И МЕТААНАЛИЗ
ПИ. Карибаева, 2Б.Турдалиева, 3 Нор Зураида Зайнал, 4Ф. Багиярова
1 2 Казахский медицинский университет непрерывного образования, г. Алматы 3 Малайский университет, Куала-Лумпур, Малайзия 4 Казахский Национальный медицинский университет им.С.Д. Асфендиярова, г. Алматы
АННОТАЦИЯ
Введение. Тревожность у пациентов с метастатическим или рецидивирующим раком молочной железы является частой психологической коморбидностью. Это исследование направлено на систематический обзор литературы по обсервационным исследованиям с данными о распространенности тревожности у пациентов с метастатическим и рецидивирующим раком молочной железы, изучение объединенной средней распространенности тревожности и потенциальных источников неоднородности.
Методы. Был проведен обширный систематический обзор баз данных PubMed, Web of Science, ScienceDirect, Google Scholar и Open Grey, а также последующий ручной поиск литературы по списку ссылок включенных исследований.
Результаты. Мы определили 16 подходящих исследований, в которых было оценено наличие тревожности у 1284 пациентов, используя структурированное интервью и два вида опросников для само-заполнения. Всего критериям тревожности соответствовал 371 пациент. Согласно модели случайных эффектов, объединенное среднее значение распространенности тревожности составило 29,93% (95% ДИ [23,22; 37,09]; I2 = 86%). Исследования, в которых сообщалось о распространенности тревожности за последние пятнадцать лет, имели такой же уровень, как и исследования, опубликованные за пятнадцать лет до этого.
Ограничения. Были включены только исследования на английском языке; ни одно исследование из регионов Африки и Юго-Восточной Азии не соответствовало критериям включения в систематический обзор; у нас не было достаточно данных о времени между постановкой диагноза рака молочной железы и оценкой тревожности; гетерогенность включенных исследований была высокой.
Выводы. Примерно у одной трети пациентов с распространенным раком молочной железы диагностируется тревожность. Высокие психологические потребности пациентов с раком молочной железы должны быть адресованы не только при первичной диагностике, но также при рецидиве и прогрессировании заболевания.
Ключевые слова: рак молочной железы, тревожность, метастатический, рецидивирующий, систематический обзор. g
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