Table 3.
RS Interventions With PNI Measures in Breast Cancer Survivors.
| No. | Study (First Author, Year) | Design | Cancer Stage | Intervention Group (IG) (n) vs Control Group (CG) (n) | Intervention Duration | Psychosocial and RS Measures | Objective (PNI) Measures | Key Health Outcomes |
|---|---|---|---|---|---|---|---|---|
| 1 | Nunes (2007)71 | RCT | I-II | Relaxation/visualization (IG) (RVT)* (n = 20) vs CG: Assessment only* (n = 14) *All participants undergoing concurrent radiotherapy |
24 consecutive days, 30-min sessions | Stress, Anxiety, Depression (ISSL, STAI, BAI, BDI) | Cortisol | RVT improved depression and anxiety scores (P < .05). Change in anxiety negatively correlated with cortisol (r = −0.38). RVT had no effect on cortisol levels |
| 2 | Witek-Janusek (2008)105 | Non-RCT | 0-II | MBSR (IG) (n = 38) vs CG: Assessment only (n = 28) |
8 weeks; 150 min/wk | Quality of Life, Coping, Mindfulness (QOLI-cv3, JCS, MAAS) | Lymphocytes, NKCA, Cytokines (Interleukin [IL])-2, IL-4, IL-6, IL-10, and interferon-gamma (IFN-γ), cortisol | MBSR group had lower levels of NKCA, IL-4, IL-6, IFN-γ (all P < .04) compared with CG. cortisol was lower in MBSR group (P = .002) than CG. No effect on mindfulness (P > .05). Treatment group reestablished positive immune function while control group had continued immune dysregulation |
| 3 | Lengacher (2008)74 | RCT | 0-II | Guided imagery (IG) (n = 15) vs Usual care CG (n = 13) |
6-7 weeks (2-3 weeks preop through 4 weeks postop) | None | Natural killer (NK) cells, cytokine (IL-2) | Guided imagery positively influenced NK cell cytotoxicity after IL-2 activation at 4 weeks postoperative compared with CG (P < .05) |
| 4 | Rao (2008)79 | RCT | II-III | Yoga (IG) (n = 33) vs Supportive therapy and exercise CG (n = 36) |
4 weeks | (Anxiety, Depression, Function) (STAI, BDI, FLIC) |
T-lymphocyte subsets, CD4%, CD8%, NK cells, and immunoglobulin (IgA, IgG, IgM) | Yoga group demonstrated decreased anxiety (P = .04), depression (P = .01), decreased symptom severity (P = .01), decreased distress (P < .01) and improved QOL (P = .01) compared with CG. Less immune dysfunction was observed in yoga group (decreased CD56%, P = .02) and (decreased IgA, P = .001) compared with CG |
| 5 | Phillips (2008)106 | RCT | 0-III | CBSM (IG) (n = 65) vs 1-day education CG (n = 63) |
10 weeks; repeat measures over 12 months | Current Status (MOCS-Relaxation) | Cortisol | Greater reductions in cortisol levels across 12 months in CBSM compared with CG, although effect was small (d = 0.20). |
| 6 | Antoni (2009)107 | RCT | 0-III | CBSM (IG) (n = 65) vs Usual care CG: 1-day education (n = 63) |
10 weeks | Stress, Anxiety & Depression, & Negative Mood (IES, HADS, ABS) |
Cortisol, lymphocyte subsets, cytokines (IL-2, IFN-γ, IL-4) | CBSM had improved cortisol patterns (P < .01), improved IL-2 (P < .05), and improved IFN-γ (P < .01) function compared with CG during the first 6 months. Results suggest CBSM group may have experienced a buffering effect of adjuvant therapy compared with the CG. Improved trends observed in psychosocial measures; however, no significant effects observed between changes in psychosocial measures and biomarker measures |
| 7 | Eremin (2009)72 | RCT | II-IV | Relaxation and guided imagery (IG) (n = 40) vs Standard care CG (n = 40) |
37 weeks | None | T-cell subsets and lymphokine activated killer cells, B lymphocytes and monocytes; cytokines IL-1beta (1β), IL-2, IL-4 and IL- 6 and TNF-α | At 8 weeks, significant correlations observed between imaging ratings and natural killer cell activity (r = 0.319, P = .02). Relaxation frequency (r = 0.308, P = .018) and imagery ratings (r = 0.308, P = .019) correlated significantly with blood IL-1β, CD4+, and CD8+ levels. |
| 8 | Vadiraja (2009)108 | RCT | I-III | Yoga (IG) (n = 44)* vs Supportive therapy CG* (n = 44) *All participants undergoing concurrent radiotherapy |
6 weeks (3) 1-hour sessions per week |
Anxiety & Depression, Stress (HADS, PSS) |
Cortisol | Positive correlations between decreased AM cortisol levels and decreased anxiety (Cohen’s f = 0.31), depression (f = 0.31), and stress (f = 0.36) in yoga group compared with CG |
| 9 | Matchim (2010)109 | Non-RCT | 0-II | MBSR (IG) (n = 15) vs Wait list CG (n = 17) |
8 weeks 90 min/wk Repeat measures at 1 month |
Mood, Stress, Mindfulness (POMS, C-SOSI, FFMQ) | Salivary cortisol, blood pressure (BP), pulse, and respirations | Increased mindfulness decreased BP, pulse, and respirations observed in MBSR compared with CG (P = .05 to P = .001). Initial decrease in AM cortisol within MBSR group was statistically significant (P < .05), but was not sustained at 1-month follow-up |
| 10 | Lengacher (2013)50 | RCT | 0-III | MBSR (IG) (n = 42) vs Usual care CG (n = 40) |
6 weeks 2 h/wk Repeat measures at 12 weeks |
None | Lymphocyte subsets, T helper 1 and 2 cells (Th1/Th2), NK cells, IFN-γ, IL-4 | Positive associations between all immune subset recoveries in MBSR group compared with CG. Women who received MBSR had T cells more readily activated by the mitogen phytohemagglutinin and an increase in the Th1/Th2 ratio (P = .002). MBSR associated with a more rapid return to normal immune function compared with CG, particularly in early posttreatment recovery periods |
| 11 | Hsiao (2012)104 | RCT | 0-III | Body-mind-spirit (BMS) (IG) (n = 26) vs Education CG (n = 22) |
8 weeks 2 h/wk Repeat measures at 5 and 8 months |
Depression Meaning in Life (Purpose, Search) (BDI, MLQ-P, MLQ-S) |
Cortisol | At 5 months, BMS was related to greater spiritual growth (search for meaning in life) (P < .01). At 8 months, the BMS group demonstrated healthier cortisol patterns compared with CG (P < .05). |
| 12 | Branstrom (2012; 2013)110,111 | RCT | Data not provided | MBSR (IG) (n = 32) vs Wait list CG (n = 39) |
8 weeks 2 h/wk Repeat measures at 3 and 6 months |
Stress, Anxiety & Depression, Mood, Coping; Mindfulness (PSS, HADS, IES-R, PSOM, CSES, FFMQ) |
Cortisol | MBSR associated with lower stress (P = .06), lower anxiety (P = .09), and increased mindfulness (P < .01). Although not quite significant (r = −0.38, P = .06) a trend was observed that MBSR demonstrated a moderate effect on awakening cortisol levels and was sustained at 6-month follow-up. Nonsignificant effects between stress and cortisol (P = .06) were observed |
| 13 | Campbell (2012)92 | NonRCT | Data not provided | MBSR (IG) (n = 19) vs Wait list CG (n = 16) |
8 weeks 90 min/wk |
Mindfulness, Rumination (MAAS, RRQ-rs) | Blood pressure (BP) | MBSR may improve mindfulness, moderate effect between decreased rumination and decrease systolic BP (r = 0.35), no main effects observed |
| 14 | Carlson (2013)68 | RCT | 0-IV | MBCR (IG) (n = 113) vs Supportive emotional therapy (SET) (IG) (n = 104) vs Usual care CG: 1-day stress management seminar (n = 54) |
8 weeks 90 min/wk |
Mood, Stress, Quality of Life, Social Support (POMS-TMD, C-SOSI, FACT-B, FACT-G, MOS-SSS) |
Cortisol | Cortisol patterns were stable over time in both SET (P = .003) and MBCR (P = .014) groups relative to the CG, who had more flattened cortisol slopes. Women in MBCR improved more over time on stress symptoms compared with both SET (P = .009) and control (P = .023) groups. Greater improvements in MBCR group in quality of life compared with SET (P = .006) and CG (P = .005); and in social support compared with the SET (P = .012) |
| 15 | Chen (2013)112 | RCT | 0-III | Qigong (IG) (n = 49)* vs Wait list CG (n = 47)* *Participants currently undergoing radiotherapy |
5 weeks 40 min/wk with 1- and 3-month repeat measures |
Depression, Fatigue, Quality of Life, Sleep Disturbance (CES-D, BFI, FACT-G, PSQI) |
Cortisol | Qigong group reported less depression over time than women in CG (P = .05). Women who had elevated depressive symptoms at the start of radiotherapy reported less fatigue (P < .01) and better overall quality of life (P < .05) in the Qigong group compared with the CG. No significant changes observed in cortisol slopes |
| 16 | Robins (2013)77 | RCT | I-IIIa | (n = 109)* (no further data) Tai Chi (IG) vs Spiritual growth group (IG) vs Usual care CG *Concurrent chemotherapy |
10 weeks 90 min/wk Repeat measures at 1 week, 4.5 months, 6 months |
Stress, Quality of Life, Depression (IES, FACT-B, CES-D) |
Cytokine panel (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, TNF-α) | Interesting patterns in biomarkers observed; however, no statistically significant effects observed between intervention and control groups while currently receiving chemotherapy |
| 17 | Reich (2014)113 | RCT | 0-III | MBSR (IG) (n = 17) vs Usual care/wait list CG (n = 24) |
6 weeks 2 hs/wk Measures at baseline and 6 weeks |
Symptoms (MDASI) |
Lymphocyte subsets, mitogen-stimulated subsets, cytokines | After 6 weeks, multiple baseline biomarkers were significantly positively improvement in GI symptoms (P = .035) and fatigue (P = .035) in MBSR group. Regression modeling identified B-lymphocytes and IFN-γ as the strongest predictors of gastrointestinal symptom improvement (P < .01). CD4+, CD8+ were predictive of strongest predictor of cognitive/ psychological improvement (P = .02). Lymphocytes and IL-4 were strongest predictors of fatigue improvement (P < .01) |
| 18 | Bower (2012; 2014)78,114 | RCT | 0-II | Iyengar yoga (IG) (n = 14) vs Usual care CG (n = 15) |
12 weeks 90 min, twice weekly Repeat measures at baseline, 12 weeks, and 24 weeks |
Fatigue, Depression, Sleep, Stress, Vigor (FSI, BDI-II, PSQI, PSS, MSFI) |
Cortisol, tumor necrosis factor-alpha (TNF-α), IL-1, IL-6, CRP | Decreased fatigue in yoga group from baseline to posttreatment and sustained at 3-month follow-up compared to CG (P = .032). Yoga group had significant increases in vigor compared with CG (P = .011). Both groups had positive changes in depressive symptoms and perceived stress (P < .05). Yoga group showed improved immune biomarker functioning compared with controls (P < .05). Tumor necrosis factor patterns remained stable in yoga group, while CG levels increased (P = 0.28). Similar trend observed with IL-1, but nonsignificant (P = .16). No significant changes in CRP, IL-6 or diurnal cortisol patterns |
| 19 | Chandwani (2014)115 | RCT | 0-III | Yoga (IG) (n = 53)* vs Stretching (IG) (n = 56)* vs Wait list CG (n = 54)* *Concurrently undergoing radiotherapy |
6 weeks Up to 180 min/wk Repeat measures at 1, 3, and 6 months postintervention |
Quality of Life, Fatigue, Depression, Sleep (MO-SF 36, BFI, CES-D, PSQI) |
Cortisol | Yoga group demonstrated greater increases in physical component scale scores compared with CG at 1 and 3 months after radiotherapy (P = .01 and P = .01, respectively). At 1, 3, and 6 months, the yoga group had greater increases in physical functioning compared with both stretching and CG (P < .05), with stretching and CG differences at only 3 months (P < .02). Yoga and stretching groups had reduced fatigue (P < .05) at radiotherapy completion. No group differences for mental health and sleep quality. Cortisol slope was steepest for the yoga group compared with the stretching and CG at the end (P = .023 and P = .008, respectively) and 1 month after radiotherapy completed (P = .05 and P = .04, respectively) |
| 20 | Kiecolt-Glaser (2014)116 | RCT | 0-IIIa | Yoga (IG) (n = 100) vs Wait list CG (n = 100) |
12 weeks 90 min/twice weekly Repeat measures at 3 months postintervention |
Fatigue, Quality of Life, Depression, Sleep, Activity, Diet (MFSI-SF, MO SF-36, CES-D, PQSI, CHAMPS, FFQ) |
Cytokines (IL-1β, IL-6, TNF-α) | At posttreatment, fatigue was not lower in yoga compared with CG (P > .05) but vitality was higher (P = .01). At 3 months posttreatment, fatigue was lower in the yoga group (P = .002), vitality was higher (P = .01), and IL-6 (P = .027), TNF-α (P = .027), and IL-1 (P = .037) were lower for yoga group compared with CG. No group differences in depression at either time points (P > .20). Frequency of yoga practice showed a stronger association with fatigue and vitality, but not depression; greater changes associated with more frequent practice. At 3 months posttreatment, increased yoga practice was associated with decreased IL-6 (P = .01) and IL-1 (P = .03), but not TNF-α production (P > .05) |
| 21 | Lengacher (2014)117 | RCT | 0-III | MBSR (IG) (n = 74) vs Usual care (n = 68) |
6 weeks intervention Repeat measures at 12 weeks |
Recurrence Concerns, Mindfulness, Stress, Anxiety, Depression (CARS,CAMS, PSS, STAI, CES-D) |
Telomere length, telomere activity | Telomere activity (TA) increased steadily over 12 weeks in MBSR group (17%) compared with minimal increase in CG (approximately 3%, P < .01). No effects observed on Telomere length (P = .92). MBSR appears to increase TA in peripheral blood mononuclear cells. TA was not associated with change in mindfulness, stress, anxiety, or fear of recurrence |
| 22 | Carlson (2015)118 | RCT | I-III | MBCR (IG) (n = 53) vs Supportive emotional therapy group (SET) (IG) (n = 49) vs Usual care (n = 26) (1-day seminar) |
8 weeks 90 min/wk plus 6-hour, 1-day retreat 12 weeks 90 min/wk 1-day, 6-hour, stress management seminar |
Mood, Stress (POMS, C-SOSI) |
Telomere length | No correlations between measures of mood (P = .80) and stress (P = .24) and changes in telomere length between MBCR and SET groups and the CG (P = .28), or across the 2 intervention conditions (P = .31) and (P = .55). Telomere length in the MBCR and SET groups remained preserved (positive outcome) while a decrease among the CG was significant (P = .04) |
Abbreviations: RS, religious and spiritual; PNI, psychoneuroimmunological; RCT, randomized control trial group; IG, intervention group; CRP, C-reactive protein; CG, control group; RVT, relaxation and visualization therapy; ISSL, Inventory of Stress Symptoms Lipp; STAI, State-Trait Anxiety Inventory; BAI, Beck Anxiety Inventory; BDI, Beck Depression Inventory; non-RCT, nonrandomized control trial group; MBSR, mindfulness-based stress reduction; QOLI-v3, Quality of Life Index Cancer Version 3, JCS, Jaloweic Coping Scale; MAAS, Mindfulness Attention Awareness Scale; FLIC, Functional Living Index of Cancer; MOCS-R, Measure of Current Status–Relaxation; IES, Impact of Events Scale; HADS, Hospital Anxiety and Depression Scale; ABS, Affects Balance Scale; PSS, Perceived Stress Scale; POMS, Profile of Mood States; C-SOSI, Calgary Symptoms of Stress Inventory; FFMQ, Five Facet Mindfulness Questionnaire; MDASI, MD Anderson Symptom Inventory; MLQ-P, Meaning in Life Questionnaire, Presence; MLQ-S, Meaning in Life Questionnaire; IES-R, Impact of Events Scale–Revised; PSOM, Positive State of Mind; CSES, Coping Self-Efficacy Scale; RRQ-rs, Rumination Reflection Questionnaire—revised; MBCR, mindfulness-based cancer recovery; POMS-TMD, Profile of Mood States–Total Mood Disturbance; FACT-B, Functional Assessment of Cancer Therapy–Breast; FACT-G, Functional Assessment of Cancer Therapy–General; MOS-SSS, Medical Outcomes Study–Social Support Survey; SOSI, Symptoms of Stress Inventory; NK, natural killer; IFN-γ, interferon-gamma; IL, interleukin; DHEA, dehydroepiandrosterone sulfate; FACIT-G, Functional Assessment of Cancer Illness Therapy–General; CES-D, Center for Epidemiological Studies–Depression Scale; BFI, Brief Fatigue Inventory; PSQI, Pittsburg Sleep Quality Index; FSI, Fatigue Symptom Inventory; BDI-II, Beck Depression Inventory–II; MFSI, Multidimensional Fatigue Symptom Inventory; MO SF-36, Medical Outcomes Short-Form 36; CHAMPS, Community Healthy Activities Model Program for Seniors; FFQ, Food Frequency Questionnaire; CARS, Concerns About Recurrence Scale; CAMS, Cognitive and Affective Mindfulness Scale–Revised.