Breast cancer affects both men and women. However, men have a low rate of breast cancer, and the lifetime risk for American men is approximately 1 in 1000. By contrast, 1 in 8 women will develop breast cancer throughout their lives; therefore, the risk of breast cancer is an overwhelmingly greater burden for women.1,2 For example, Hampton and Frombach3 found that, after cancer treatment, women pay more attention to work, are affected more by economic pressure, and have more intense interpersonal relationships compared with men. The problem of female breast cancer requires urgent attention and solutions; thus, this study focused on female patients with breast cancer.

Breast cancer poses a huge health and economic burden on individuals and society. A diagnosis of cancer increases healthcare expenditure because of the incidence of health conditions such as mental illness, pain, and poor sleep quality. In addition, the disease exerts financial burden through personal disability, morbidity, and reduction in workdays, resulting in lower economic productivity and growth. Because of advances in treatment and diagnostic techniques enabling early detection, breast cancer mortality is declining. However, traditional chemotherapy and radiation therapy have numerous adverse effects. Breast cancer survivors often develop co-occurring symptoms with cancer treatments, such as fatigue, depression, anxiety, stress, and pain, which can last for months or even years after the treatment is concluded.4–6 Therefore, they should opt for complementary alternative therapies such as art therapy, music therapy, horticultural therapy, and mindfulness-based stress reduction (MBSR). Among these therapies, MBSR is the most widely used and is applicable to all activities of daily living.

Mindfulness-based stress reduction is an 8-week evidence-based program originally developed in the 1970s by Professor Jon Kabat-Zinn7 at the University of Massachusetts Medical School. Stress reduction through developing mindfulness, which entails a nonjudgmental, accepting, momentary awareness, is at the core of MBSR. Many studies have shown that the MBSR program is not only an effective method for alleviating the psychological and physiological symptoms of female breast cancer patients8–10 but also cost-effective for patients participating in high-quality randomized controlled trials (RCTs).11,12

The findings of previous studies on MBSR are inconsistent. For example, Castanhel and Liberali13 reviewed 2 RCTs and found that the fatigue results were not significant but showed a moderate effect of MBSR. Conversely, Zhang et al14 reviewed 14 RCTs and reported statistically significant results for fatigue. The evaluation time in previous studies has also been inconsistent; some studies have used short-term follow-up times of 6, 8, and 12 weeks,9,15 and some have had long-term follow-up times (eg, 6 months, 1 year, and 2 years).16,17 However, in previous MBSR meta-analyses, it has not been specified whether the data collected after the intervention were short- or long-term data.13,14 In the current study, an updated systematic review and meta-analysis was performed, and data at 2 time points, namely, the end of the intervention and 3 months after baseline, were pooled to evaluate the relationship between MBSR interventions and breast cancer symptoms. All previous clinical trials were integrated to clarify the reported inconsistencies.

Research Question

This research was guided by the following specific research question: What are the effects of MBSR interventions on clinical, psychological, physiological, and quality-of-life outcomes in patients with breast cancer?

Materials and Methods Database and Search Strategy

This review was designed and conducted with reference to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (Table S1).18 We (Y.C.C. and W.Y.H.) searched for relevant literature on the PubMed, EMBASE/MEDLINE, PubMed Central, and National Digital Library of Theses and Dissertations in Taiwan databases from inception to April 2020, and we also reviewed the reference lists in the publications. We included all RCTs and used the following search terms: “breast,” “breast cancer,” “breast neoplasms,” “MBSR,” “mindful,” and “mindfulness.” For the National Digital Library of Theses and Dissertations in Taiwan database, we used the following Chinese search terms: ru yan (English translation: breast cancer), jheng nian jian ya (MBSR), and jheng nian (mindful). All possible disagreements were resolved through discussions with a third author (T.L.Y.).

Inclusion and Exclusion Criteria

We placed no restrictions on language to ensure a comprehensive search. All authors possess literacy skills in Chinese and English. Inclusion criteria for the RCT studies were based on the participants, interventions, comparators, outcomes, and study type (PICOS) framework. We included women with breast cancer who had received MBSR therapy and compared them with controls. Moreover, the outcomes of interest were fatigue, depression, anxiety, quality of life, mindfulness, stress, fear of recurrence, sleep quality, pain, sexual function, and psychoimmunological factors. Studies were excluded if they were non-RCT, nonhuman, and observational studies, and conference abstracts were also excluded.

Data Extraction and Quality Assessment

The 2 authors (Y.C.C. and W.Y.H.) independently performed data extraction and coding on all included studies, and the following data were collected: the first author's name; country of research; the number of patients, patient mean age, and patient cancer stage; MBSR protocol; follow-up time; outcome variables; and results. We only trusted the data published in the article in the entire process of extracting data. We extracted the mean and standard deviation (SD) at baseline, end of intervention, and up to 3 months after the baseline outcome of the MBSR and control groups as well as the number of patients in each group. In case of incomplete data, we contacted the author, but we were unable to obtain the raw data. We used the Cochrane risk-of-bias assessment tool to assess the included RCTs.19

Statistical Analysis

We used Cochrane Collaboration Review Manager 5.320 (Cochrane Community, London, United Kingdom) to perform statistical analyses. Furthermore, we pooled data at baseline, end of intervention, and up to 3 months after baseline. If the evaluation tools for the results differed, we used the standardized mean difference (SMD) to determine the effect size; conversely, if the evaluation tools were the same, the effect size of the mean difference (MD) with 95% confidence interval (CI) was used to summarize our continuous outcomes. Assuming that the true effect size was not the same, we applied the random-effects meta-analytic model of DerSimonian and Laird21 because of the clinical and statistical heterogeneity in our included trials. The random-effects model introspects various sources of variability or heterogeneity; thus, we deployed it within and between all included studies in which variability existed in research design, sample size, or tools used to measure outcomes. Furthermore, we assessed statistical heterogeneity using the Cochrane Q statistic and calculated the proportion of total variability in point estimates using the I2 statistic; the I2 value ranges between 0% and 100%. Low, moderate, and high heterogeneity are usually defined as I2 values of 25%, 50%, and 75%, respectively. A P value less than .05 indicated statistical significance. We detected publication bias by inspecting the symmetry of funnel plots.

Results Description of Studies and Quality Assessment

We identified 873 articles in the search, and after removing 822 duplicates, 24 articles were selected, and their titles, abstracts, and contents were screened. Twenty-seven studies were identified as eligible for full-text screening. The reasons for exclusion comprised the absence of full text and the presence of non-MBSR intervention measures, qualitative studies, single groups, and mixed-method designs. The reference lists of journal articles were checked, after which the relevant articles were manually searched. Nineteen studies met our inclusion criteria and were included in the systematic review, among which 10 articles had complete data and were included in our meta-analysis. The search algorithm is presented in Figure 1.22

Figure 1:

Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Descriptive Characteristics of Participants

Patients with breast cancer were aged 43 to 58 years with diagnosis stages of 0 to 4; the numbers of participants ranged from 36 to 322. In particular, 1 article included patients with metastatic breast cancer; however, its daily performance score was 0 to 2.23 Participants had undergone total mastectomy, lumpectomy, chemotherapy, radiation therapy, and hormonal therapy (see Table).

Table - Characteristics of Trials Included in the Meta-analysis Author (Year), Country Participants Intervention Protocol Control Group Follow-up Outcome Variables Results Witek Janusek et al15 (2019), United States n = 192
Mean age, 55 y
Stages 0-III n = 63, MBSR 8 wk, 2.5 h/wk; 6-h silent mindful retreat after the fifth week n = 61, ACC Baseline, 4 and 8 wk, 1 and 6 mo Blood for NKCA, TNF-α, and interleukin (IL)-6; IFN-γ Significant:
Rapid restoration of NKCA, accompanied with lower circulating TNF-α levels, lower IL-6 production, and greater IFN-γ production Lengacher et al10 (2019), United States n = 322
Mean age, 56.6 y
Stages 0-III n = 167, MBSR 6 wk, 2 h/wk n = 155, UC Baseline, 6 wk Cortisol, IL-6, CES-D, STAI, PSS, PSQI, FSI, SF-36 Significant:
Reduced IL-6 and salivary cortisol Park et al24 (2019), United States n = 185
Mean age, 58.2 y
Stages 0-III n = 92, MBSR (BC) program 6 wk, 2 h/wk n = 93, UC Baseline, 6 wk, and 12 wk SNPs In the MBSR program, 3 SNPs have the strongest and most consistent effects on mitigating the effects of symptoms (rs4680 in COMT, rs6314 in HTR2A, and rs429358 in APOE). Kenne Sarenmalm et al25 (2017), Sweden n = 166
Mean age, 57.2 y
Stage not written n = 62, MBSR; n = 52, active controls MBSR (8 wk self-instructing MBSR program + instructor and weekly group sessions); active controls (8 wk self-instructing MBSR program) n = 52, non-MBSR Baseline, 3 mo HADS, MSAS, TMSAS, GDI, SF-36, SOC, FFMQ, PTGI
Lymphocyte distribution in peripheral blood, NKCA, cytokine Significant:
Improvements in depression, distress, symptom burden, and mental health and increased NK-cells and B cells
Not statistically significant:
IL-6 or IL-8 Reich et al26 (2017), United States n = 322
Mean age, 51 y
Stage 0/I vs II/III n = 152, MBSR 6 wk, 2 h/wk n = 147, UC Baseline, 6 and 12 wk IL-1β, IL-6, IL-10, TNF-α, TGF-β1, soluble tumor necrosis factor receptor 1 Increases in TNF-α and IL-6 during weeks 6 and 12 rather than at the baseline and week 6
Not statistically significant:
TNFR1 levels across the 12-wk program Reich et al27 (2017), United States n = 322
Mean age, 56.6 y
Stages 0-III n = 167, MBSR 6 wk, 2 h/wk; meditative techniques for 15–45 min/d and to record their practice times in a daily diary n = 155, UC Baseline, 6 and 12 wk CARS, ESDS, STAI, PSS, CAMS-R, MDASI, PSQI, FSI, BPI, ECOG, SF-36 Baseline: pain (not statistically significant by MBSR), psychological and cognitive issues and fatigue
Week 6: MBSR effectiveness in anxiety, depression, perceived stress and QOL, emotional well-being, fatigue, sleep, and drowsiness Johns et al16 (2016), United States n = 71; breast cancer (n = 60) and colorectal cancer (n = 11)
Mean age, 56 y
Stages 0-III n = 35, MBSR 8 wk; 2 h/wk + home meditation practices were 20 min. n = 36, fatigue education and support (ES) Baseline (T1), 8 wk (T2), and 6 mo (T3) AFI Improvements mediated by mindfulness in the AFI total score at T2 and T3 (eg, MBSR vs ES) among the groups Lengacher et al28 (2016), United States n = 322
Mean age, 56.6 y
Stages 0-III n = 167, MBSR 6 wk, 2 h/wk + homework assigned 15–45 min of meditative techniques n = 155, UC Baseline, 6 wk BPI, FSI, CES-D, STAI, PSS, CARS, SF-36 Anxiety, fear of recurrence and associated problems, physical symptoms of severe fatigue and fatigue interference, and greatest benefit of stress Wurtzen et al29 (2015), Denmark n = 336
Mean age, 54.1 y
Stages I-III n = 168, MBSR 8 wk, 2 h/wk + 45-min daily home practice n = 168, UC Baseline, 8 wk, 6 and 12 mo BCPT, SCL-90-R, FFMQ, FACIT-Sp Significant:
During follow-up after 6 mo
1. Symptom burden↓
2. Distress↓
3. Mindfulness skills↑
4. Spiritual well-being↑
Not statistically significant:
During follow-up after 12 mo Bower et al30 (2015), United States n = 71
Mean age, 46–47 y
Stages 0-III n = 39
Mindful awareness practices 6 wk, 2 h/wk + 5–20 min/d n = 32
Wait-list control Baseline, 6 and 12 wk PSS, CES-D, FSI, PSQI, BCPT, QLACS, IES, PANAS-PA, FACIT Significant reductions in perceived stress, reductions in proinflammatory gene expression, and inflammatory signaling; reduced fatigue, sleep disturbance, and vasomotor symptoms and increased peacefulness, purpose, and positive attitude Lengacher et al31 (2015), United States n = 79
Mean age, 57 y
Stages 0-III n = 38, MBSR 6 wk,2 h/wk + homework assigned 15-45 min of meditative techniques n = 41, UC Baseline, 6 and 12 wk Objective sleep parameters: Actiwatch
Subjective sleep parameters: PSQI and sleep diaries, cortisol Objective sleep results (actigraphy) indicated greater sleep efficiency and less sleep disturbance in MBSR(BC) participants compared with UC participants. Lengacher et al32 (2014), United States n = 142
Mean age, 55.3 y
Stages 0-III n = 70, MBSR 6 wk,2 h/wk + formally meditate 15-45 min per day + informal practice 15-45 min per day n = 64, UC Baseline, 6 and 12 wk Blood samples: telomere length (TL) and telomerase activity (TA), CARS, ESDS, STAI, PSS, CAMS-R TA increased steadily in the course of 12 wk in the MBSR(BC) group.
Not statistically significant:
1. TL Reich et al33 (2014), United States n = 41
Mean age, 58.2 y
Stages 0-III n = 17, MBSR 6 wk,2 h/wk + 15-45 min daily of formal and informal practice n = 24, UC Baseline, 6 wk Peripheral blood: T cells, B-lymphocytes, IFN-γ 1. B-lymphocytes and IFN-γ as the strongest predictors of gastrointestinal improvement
2. +CD4 + CD8 as the strongest predictors of cognitive/psychological improvement
3. Lymphocytes and IL-4 as the strongest predictors of fatigue improvement Lengacher et al34 (2014), United States n = 82
Mean age, 58.2 y
Stages 0-III n = 40, MBSR 6 wk,2 h/wk + 15–45 min daily of informal practice n = 42, UC Baseline, 6 wk CARS, PSS, STAI, CES-D, LOT-R, SF-36 MBSR(BC) reduces fear of recurrence and improves physical functioning, which reduces perceived stress and anxiety. Rahmani et al35 (2014), Iran n = 36
Mean age, (CG/MBSR/MCT = 44.08/43.25/43.33)
Stages I-III N = 12, MBSR 8 wk,2 h/wk n = 12, MCT
n = 12, CG Baseline, 8 wk, 2 mo QLQ-C30, QLQ-BR23 MBSR and MCT improve QoL; MBSR excels in the function role and reduces fatigue and pain. Henderson et al17 (2013), United States n = 172
Mean age, 49.8 y
Stages I-II n = 53, MBSR 8 wk, 2.5–3.5 h/wk + 7. 5-h intensive retreat session given in the sixth week n = 52,nutrition education intervention (NEP); n = 58,UC Baseline, 4 mo, and 1 and 2 y FACT-B, BDI, BPI, BAI, RSES, SCS, UCLA-LS, Mini-MAC,CECS, SCL-90-R MBSR improves QoL and psychosocial coping. Henderson et al36 (2012), United States n = 172
Mean age, 49.8 y
Stages I-II n = 53, MBSR 8 wk, 2.5-3.5 h/wk + 7.5-h intensive retreat session given in the sixth week n = 52,NEP; n = 58, UC Baseline, 4 mo, and 1 and 2 y FACT-B, BDI, BAI, SCL-90-R,UCLA-LS, Mini-MAC, SOC, CECS, SCL-90-R Significant:
Improvement in QOL and coping outcomes Wurtzen et al37 (2013), Danish n = 336
Mean age, 54.1 y
Stages I-III n = 168, MBSR 8 wk, 2 h/wk + 45-min daily home practice n = 168, UC Baseline, 8 wk, 6 and 12 mo SCL-90-R, CES-D The MBSR group showed decreased anxiety and depression. Lengacher et al38 (2012), United States n = 84
Mean age, 58 y
Stages 0-III n = 41, MBSR 6 wk,2 h/wk n = 43, UC Baseline, 6 wk MDASI The MBSR group showed reduced fatigue and sleep problems and improved symptoms after 6 wk.

Abbreviations: ACC, active control condition; AFI, Attentional Function Index; BAI, Beck Anxiety Inventory; BCPT, Breast Cancer Prevention Trial Symptom Checklist; BDI, Beck Depression Inventory; BPI, Brief Pain Inventory; CAMS-R, Cognitive and Affective Mindfulness Scale-Revised; CARS, Concerns About Recurrence Scale; CECS, Courtauld Emotional Control Scale; CES-D, Center for Epidemiologic Studies Depression Scale; CG, control group; ECOG, Everyday Cognition scale; EORTC, The European Organisation for Research and Treatment of Cancer; ESDS, Epidemiological Studies Depression Scale; FACIT-Sp, Functional Assessment of Chronic Illness Therapy–Spiritual Well-Being Scale; FACT-B, Functional Assessment of Cancer Therapy - Breast Cancer; FFMQ, Five Facet Mindfulness Questionnaire; FSI, Fatigue Symptom Inventory; GDI, Global Symptom Distress Index; HADS, Hospital Anxiety and Depression Scale; IES, Impact of Event Scale; IFN, interferon; LOT-R, Life Orientation Test-Revised; MBSR, mindfulness-based stress reduction; MCT, metacognition therapy; MDASI, M.D. Anderson Symptom Inventory; Mini-MAC, Mini-Mental Adjustment to Cancer Scale; MSAS, Memorial Symptom Assessment Scale; NKCA, natural killer cell activity; PANAS-PA, Positive and Negative Affect Schedule–Positive Affect; PSQI, Pittsburgh Sleep Quality Index; PSS, Perceived Stress Scale; PTGI, Posttraumatic Growth Inventory; QLACS, Quality of Life in Adult Cancer Survivors; QLQ-C30, Core Quality of Life questionnaire; QoL, Quality of life; RSES, Rosenberg Self-Esteem Scale; SCL-90-R, Symptom Checklist-90-Revised; SCS, Sense of Coherence Scale; SF-36, 36-item Short Form Health Survey; SOC, Sense of Coherence scale; SNPs, single-nucleotide polymorphisms; STAI, State-Trait Anxiety Inventory; TGF, transforming growth factor; TMSAS, Total Symptom Burden Scale; TNF, tumor necrosis factor; UC, usual care; UCLA-LS, UCLA Loneliness Scale.

Clinical Trial Protocol and Follow-up Interval

The standard MBSR intervention is an 8-week course with 2 to 3 hours of sessions per week, in addition to 1 day of intensive practice between the sixth and seventh weeks. However, in recent years, considering the convenience and participation rate of patients, the intervention can be completed in 6 weeks, with each session lasting 2 hours. Therefore, intensive practice (for approximately 6–7.5 hours) is arranged in the fifth week; course participants' informal homework requires 15 to 45 minutes of meditation, with an average follow-up time of approximately 6 to 18 weeks.15,24,28

Risk of Bias in Each Included Study

Figures 2 and 3 demonstrate the risk of bias for each study. The studies were indexed based on the first author's last name and year of publication. Seven domains of risk of bias were assessed for each study. For the domain of random sequence generation (selection of bias), 100% (19/19) were rated as low; for the domain of allocation concealment (selection bias), 15.8% (3/19) were rated as low and 84.2% (16/19) were rated as high; for the domain of blinding of participants and personnel (performance bias), 10.5% (2/19) were rated as low and 89.5% (17/19) were rated as high; for the domain of blinding of outcome assessment (detection bias), 100% (19/19) were rated as high; for the domain of incomplete outcome data (attrition bias), 31.6% (6/19) were rated as low, 57.9% (11/19) were rated as high, and 10.5% (2/19) were rated as unclear; for the domain of selective reporting (reporting bias), 94.7% (18/19) were rated as low and 5.3% (1/19) were rated as high; and for the domain of other bias, 100% (19/19) were rated as unclear.

Figure 2:

Cochrane risk-of-bias tool for included studies/RCTs.

Figure 3:

Cochrane risk-of-bias summary for included studies.

Publication Bias

Publication bias was assessed using a funnel plot including 11 RCTs. The funnel plot revealed no obvious asymmetry.

Data Synthesis and Meta-analysis PSYCHOLOGICAL EFFECTS

To investigate the end-of-intervention effect of MBSR on depression, 6 RCT studies with 1024 subjects were pooled for a meta-analysis. Compared with the control group, the MBSR group exhibited significantly reduced depression, with an SMD of −1.32 (95% CI, −2.18 to −0.46; P = .003, I2 = 97%). To investigate the end-of-intervention effect of MBSR on anxiety, 3 studies with 720 subjects were pooled for a meta-analysis. Compared with the control group, anxiety was not significantly reduced in the MBSR group, with an SMD of −0.05 (95% CI, −0.02 to 0.09; P = .47, I2 = 0%). To investigate the end-of-intervention effect of MBSR on stress, compared with the control group, stress was not significantly reduced in the MBSR group, with an MD of −2.34 (95% CI, −5.96 to 1.27; P = .20, I2 = 97%).

To investigate the effect of MBSR on depression 3 months after baseline, 3 RCT studies with 665 subjects were pooled for a meta-analysis. Compared with the control group, the MBSR group exhibited nonsignificantly reduced depression, with an SMD of −0.64 (95% CI, −1.39 to 0.011; P = .09, I2 = 95%). Regarding the effect of MBSR on anxiety 3 months after baseline, 2 RCT studies with 606 subjects were pooled for a meta-analysis. Compared with the control group, the MBSR group exhibited nonsignificantly reduced anxiety, with an SMD of −0.09 (95% CI, −0.25 to 0.07; P = .26, I2 = 0%). Regarding the effect of MBSR on stress 3 months after baseline, 2 RCT studies with 371 subjects were pooled for a meta-analysis. Compared with the control group, the MBSR group exhibited significantly reduced stress, with an MD of −0.79 (95% CI, −1.34 to −0.24; P = .005, I2 = 0%) (Figure 4).

Figure 4:

Forest plot illustrated the psychological effects of MBSR and control group.

PHYSIOLOGICAL EFFECTS

To investigate the end-of-intervention effect of MBSR on fatigue, 4 RCT studies with 734 subjects were pooled for a meta-analysis. Compared with the control group, the MBSR group exhibited significantly reduced fatigue, with an MD of −0.47 (95% CI, −0.59 to −0.34; P < .001, I2 = 0%). Regarding the end-of-intervention effect of MBSR on pain, 5 studies with 827 subjects were pooled for a meta-analysis. Compared with the control group, pain was nonsignificantly reduced in the MBSR group, with an SMD of −0.39 (95% CI, −0.81 to 0.03; P = .07, I2 = 85%). Regarding the end-of-intervention effect of MBSR on sleep quality, 5 RCT studies with 594 subjects were pooled for a meta-analysis. Compared with the control group, sleep quality was nonsignificantly reduced in the MBSR group, with an SMD of −0.67 (95% CI, −1.43 to 0.08; P = .06, I2 = 94%).

To investigate the effect of MBSR on fatigue 3 months after baseline, 3 RCT studies with 657 subjects were pooled for a meta-analysis. Compared with the control group, the MBSR group exhibited nonsignificantly reduced fatigue, with an MD of 0.18 (95% CI, −1.26 to 1.61; P = .81, I2 = 50%). Regarding the effect of MBSR on pain 3 months after baseline, 3 RCT studies with 683 subjects were pooled for a meta-analysis. Compared with the control group, the MBSR group exhibited nonsignificantly reduced pain, with an SMD of −0.30 (95% CI, −0.75 to 0.15; P = .19, I2 = 86%). Regarding the effect of MBSR on sleep quality 3 months after baseline, 2 RCT studies with 606 subjects were pooled for a meta-analysis. Compared with the control group, the MBSR group exhibited nonsignificantly reduced sleep quality, with an SMD of −0.51 (95% CI, −1.59 to 0.57; P = .36, I2 = 92%) (Figure 5).

Figure 5:

Forest plot illustrated the physiological effects of MBSR and control group.

EFFECTS ON QUALITY OF LIFE

Regarding the end-of-intervention effect of MBSR on quality of life, compared with the control group, quality of life was nonsignificantly reduced in the MBSR group, with an SMD (95%) of −0.03 (95% CI, −0.37 to 0.31; P = .86, I2 = 75%).

Regarding the effect of MBSR on quality of life 3 months after baseline, 2 RCT studies with 598 subjects were pooled for a meta-analysis. Compared with the control group, the MBSR group exhibited nonsignificantly reduced quality of life, with an SMD of −0.02 (95% CI, −0.18 to 0.14; P = .84, I2 = 0%) (Figure 6).

Figure 6:

Forest plot illustrated the effects of MBSR and control group on quality of life.

Discussion

The strength of our meta-analysis study is that the end-of-intervention outcomes revealed reduced depression and fatigue. Furthermore, the outcomes 3 months after baseline revealed reduced stress in the MBSR group compared with the control group. We performed a comprehensive search using 5 databases without any language restrictions, and suitable statistical analysis methods were adopted for different tools and the same tools in the literature.

Zhang et al14 demonstrated that MBSR can improve fatigue. Schell et al39 also showed that fatigue can be reduced in the short term. Our study findings are consistent with those of previous meta-analyses; moreover, this study confirmed that fatigue is significantly reduced after MBSR. In addition, results pertaining to depression and stress are consistent with those of relevant studies. After MBSR therapy, patients exhibited statistically significant improvements.14,26,29,39

However, our analysis revealed no statistically significant differences in anxiety, pain, sleep quality, or quality of life. A possible explanation is that, because of depression, fatigue and stress might be normal temporary responses to life events. Mindfulness-based stress reduction was found to be particularly useful for treating transient and fluctuating symptoms in patients with breast cancer. All the included studies had a small sample size, and the floor effect was observed32,35; further studies with larger sample sizes are required. Because pain is a concomitant symptom of physical and mental illness and a dynamic process,40,41 it has been considered a potential variable in some studies.27 One study reported that patients diagnosed at an early stage were not sensitive enough to detect a reduction in pain symptoms compared with patients at advanced cancer stages.27 However, studies have also shown that MBSR offers different degrees of improvement for different types of pain. After MBSR therapy, although patients with chronic headaches and migraines exhibited the least improvement, significant improvements in pain were detected in patients with arthritis, back/neck pain, or more than 2 comorbidities.42 Studies have provided inconsistent results for pain, and pain improvement in patients with breast cancer has not been adequately studied. The outcomes in studies might affect each other; for example, patients' pain, depression, and anxiety would affect their quality of life; thus, the outcomes are not independent of each other. Further research should not only use self-reported instruments to measure subjective outcomes but also include objective monitoring indicators to accurately measure the degree of pain improvement in patients.

Some studies have reported that MBSR has multiple effects on genetic makeup, hormones, cytokines, immunoglobulin, and neurotransmitters as well as psychological responses.24,25,33 The anxiolytic effect of MBSR is achieved through the regulation of the nervous and endocrine systems. Furthermore, MBSR may regulate the sympathetic nervous system, thereby reducing cortisol levels.10,31 In addition, MBSR may trigger activity in brain regions associated with emotional experiences and suppress anxiety levels.43,44 Despite these results, further research is required to reveal the underlying mechanisms of the anxiolytic effects of MBSR in female breast cancer survivors.

Clinical Implications

Severe anxiety and depression in patients are strong predictors of pain and fatigue.45 Therefore, early MBSR interventions can reduce anxiety in women with breast cancer and prevent these adverse consequences. Mindfulness-based stress reduction interventions are both cost-effective and practical. Moreover, they are safer compared with medications and have no significant adverse effects. Therefore, on the basis of the overall review result of the meta-analysis, breast cancer survivors are recommended to practice MBSR as part of their daily care routines to enhance their emotional regulation, attentiveness, and vitality.15,24,46

Strength and Limitations

The strength of this study is that it extracted RCT trials from 5 databases to perform a comprehensive systematic review and meta-analyses. Compared with previous reviews of 2 similar topics,13,14 our study reviewed RCTs and measured short-term changes after interventions. However, this meta-analysis also had some limitations. First, differences existed in the sample population in terms of age, race, time spent on home practice during MBSR sessions, and coexisting treatment conditions, which may explain the high heterogeneity in some results. Second, although only a small number of articles were included in the meta-analysis for each outcome, we chose RCTs with more conclusive evidence. Thereafter, we standardized the results of different levels and then compared them. Third, it might be difficult to apply the double-blind design in the Cochrane risk-of-bias summary chart because it is usually necessary to assess the patients' status at the psychological level. Thus, our study did not have effective double-blindness, but it did offer high quality in other aspects. Therefore, a high degree of heterogeneity existed in depression outcomes, but because the outcome was highly significant, this did not affect our results. In the future, we can collect more data and perform a subgroup analysis to reduce heterogeneity. Fourth, this research investigated immediate effects, but a question that remains is whether the immediate effects lasted longitudinally. More relevant long-term information on MBSR should be collected in the future.

Future Research Directions

The latest reviews and meta-analyses have provided evidence that MBSR interventions have short-term beneficial effects in women with breast cancer. In the future, more indicators such as sexual function, menopausal symptoms, and fear of recurrence should be investigated, which will produce findings that can help breast cancer survivors.

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