Mindfulness-Based Stress Reduction in Post-treatment Breast Cancer Patients: Immediate and Sustained Effects Across Multiple Symptom Clusters.

CONTEXT: Breast cancer survivors (BCS) face adverse physical and psychological symptoms, often co-occurring. Biologic and psychological factors may link symptoms within clusters, distinguishable by prevalence and/or severity. Few studies have examined the effects of behavioral interventions or treatment of symptom clusters. OBJECTIVES: The aim of this study was to identify symptom clusters among post-treatment BCS and determine symptom cluster improvement following the Mindfulness-Based Stress Reduction for Breast Cancer (MBSR(BC)) program. METHODS: Three hundred twenty-two Stage 0-III post-treatment BCS were randomly assigned to either a six-week MBSR(BC) program or usual care. Psychological (depression, anxiety, stress, and fear of recurrence), physical (fatigue, pain, sleep, and drowsiness), and cognitive symptoms and quality of life were assessed at baseline, six, and 12 weeks, along with demographic and clinical history data at baseline. A three-step analytic process included the error-accounting models of factor analysis and structural equation modeling. RESULTS: Four symptom clusters emerged at baseline: pain, psychological, fatigue, and cognitive. From baseline to six weeks, the model demonstrated evidence of MBSR(BC) effectiveness in both the psychological (anxiety, depression, perceived stress and QOL, emotional well-being) (P = 0.007) and fatigue (fatigue, sleep, and drowsiness) (P < 0.001) clusters. Results between six and 12 weeks showed sustained effects, but further improvement was not observed. CONCLUSION: Our results provide clinical effectiveness evidence that MBSR(BC) works to improve symptom clusters, particularly for psychological and fatigue symptom clusters, with the greatest improvement occurring during the six-week program with sustained effects for several weeks after MBSR(BC) training. TRIAL REGISTRATION: Name and URL of Registry: ClinicalTrials.gov. Registration number: NCT01177124.

Examination of Broad Symptom Improvement Resulting From Mindfulness-Based Stress Reduction in Breast Cancer Survivors: A Randomized Controlled Trial.

PURPOSE: The purpose of this randomized trial was to evaluate the efficacy of the Mindfulness-Based Stress Reduction for Breast Cancer (MBSR[BC]) program in improving psychological and physical symptoms and quality of life among breast cancer survivors (BCSs) who completed treatment. Outcomes were assessed immediately after 6 weeks of MBSR(BC) training and 6 weeks later to test efficacy over an extended timeframe. PATIENTS AND METHODS: A total of 322 BCSs were randomly assigned to either a 6-week MBSR(BC) program (n = 155) or a usual care group (n = 167). Psychological (depression, anxiety, stress, and fear of recurrence) and physical symptoms (fatigue and pain) and quality of life (as related to health) were assessed at baseline and at 6 and 12 weeks. Linear mixed models were used to assess MBSR(BC) effects over time, and participant characteristics at baseline were also tested as moderators of MBSR(BC) effects. RESULTS: Results demonstrated extended improvement for the MBSR(BC) group compared with usual care in both psychological symptoms of anxiety, fear of recurrence overall, and fear of recurrence problems and physical symptoms of fatigue severity and fatigue interference (P < .01). Overall effect sizes were largest for fear of recurrence problems (d = 0.35) and fatigue severity (d = 0.27). Moderation effects showed BCSs with the highest levels of stress at baseline experienced the greatest benefit from MBSR(BC). CONCLUSION: The MBSR(BC) program significantly improved a broad range of symptoms among BCSs up to 6 weeks after MBSR(BC) training, with generally small to moderate overall effect sizes.

Baseline immune biomarkers as predictors of MBSR(BC) treatment success in off-treatment breast cancer patients.

Researchers focused on patient-centered medicine are increasingly trying to identify baseline factors that predict treatment success. Because the quantity and function of lymphocyte subsets change during stress, we hypothesized that these subsets would serve as stress markers and therefore predict which breast cancer patients would benefit most from mindfulness-based stress reduction (MBSR)-facilitated stress relief. The purpose of this study was to assess whether baseline biomarker levels predicted symptom improvement following an MBSR intervention for breast cancer survivors (MBSR[BC]). This randomized controlled trial involved 41 patients assigned to either an MBSR(BC) intervention group or a no-treatment control group. Biomarkers were assessed at baseline, and symptom change was assessed 6 weeks later. Biomarkers included common lymphocyte subsets in the peripheral blood as well as the ability of T cells to become activated and secrete cytokines in response to stimulation with mitogens. Spearman correlations were used to identify univariate relationships between baseline biomarkers and 6-week improvement of symptoms. Next, backward elimination regression models were used to identify the strongest predictors from the univariate analyses. Multiple baseline biomarkers were significantly positively related to 6-week symptom improvement. The regression models identified B-lymphocytes and interferon-γ as the strongest predictors of gastrointestinal improvement (p < .01), +CD4+CD8 as the strongest predictor of cognitive/psychological (CP) improvement (p = .02), and lymphocytes and interleukin (IL)-4 as the strongest predictors of fatigue improvement (p < .01). These results provide preliminary evidence of the potential to use baseline biomarkers as predictors to identify the patients likely to benefit from this intervention.

Randomized trial using gonadotropin-releasing hormone agonist triptorelin for the preservation of ovarian function during (neo)adjuvant chemotherapy for breast cancer.

PURPOSE: Chemotherapy-induced amenorrhea is a serious concern for women undergoing cancer therapy. This prospective randomized trial evaluated the use of gonadotropin-releasing hormone (GnRH) analog triptorelin to preserve ovarian function in women treated with chemotherapy for early-stage breast cancer. PATIENTS AND METHODS: Premenopausal women age 44 years or younger were randomly assigned to receive either triptorelin or no triptorelin during (neo)adjuvant chemotherapy and were further stratified by age (< 35, 35 to 39, > 39 years), estrogen receptor status, and chemotherapy regimen. Objectives included the resumption of menses and serial monitoring of follicle-stimulating hormone (FSH) and inhibin A and B levels. RESULTS: Targeted for 124 patients with a planned 5-year follow-up, the trial was stopped for futility after 49 patients were enrolled (median age, 39 years; range, 21 to 43 years); 47 patients were treated according to assigned groups with four cycles of adriamycin plus cyclophosphamide alone or followed by four cycles of paclitaxel or six cycles of fluorouracil, epirubicin, and cyclophosphamide. Menstruation resumed in 19 (90%) of 21 patients in the control group and in 23 (88%) of 26 in the triptorelin group (P= .36). Menses returned after a median of 5.8 months (range, 1 to 19 months) after completion of chemotherapy in the triptorelin versus 5.0 months (range, 0 to 28 months) in the control arm (P= .58). Two patients (age 26 and 35 years at random assignment) in the control group had spontaneous pregnancies with term deliveries. FSH and inhibin B levels correlated with menstrual status. CONCLUSION: When stratified for age, estrogen receptor status, and treatment regimen, amenorrhea rates on triptorelin were comparable to those seen in the control group.

Randomized controlled trial of mindfulness-based stress reduction (MBSR) for survivors of breast cancer.

OBJECTIVES: Considerable morbidity persists among survivors of breast cancer (BC) including high levels of psychological stress, anxiety, depression, fear of recurrence, and physical symptoms including pain, fatigue, and sleep disturbances, and impaired quality of life. Effective interventions are needed during this difficult transitional period. METHODS: We conducted a randomized controlled trial of 84 female BC survivors (Stages 0-III) recruited from the H. Lee Moffitt Cancer and Research Institute. All subjects were within 18 months of treatment completion with surgery and adjuvant radiation and/or chemotherapy. Subjects were randomly assigned to a 6-week Mindfulness-Based Stress Reduction (MBSR) program designed to self-regulate arousal to stressful circumstances or symptoms (n=41) or to usual care (n=43). Outcome measures compared at 6 weeks by random assignment included validated measures of psychological status (depression, anxiety, perceived stress, fear of recurrence, optimism, social support) and psychological and physical subscales of quality of life (SF-36). RESULTS: Compared with usual care, subjects assigned to MBSR(BC) had significantly lower (two-sided p<0.05) adjusted mean levels of depression (6.3 vs 9.6), anxiety (28.3 vs 33.0), and fear of recurrence (9.3 vs 11.6) at 6 weeks, along with higher energy (53.5 vs 49.2), physical functioning (50.1 vs 47.0), and physical role functioning (49.1 vs 42.8). In stratified analyses, subjects more compliant with MBSR tended to experience greater improvements in measures of energy and physical functioning. CONCLUSIONS: Among BC survivors within 18 months of treatment completion, a 6-week MBSR(BC) program resulted in significant improvements in psychological status and quality of life compared with usual care.

Immune responses to guided imagery during breast cancer treatment.

BACKGROUND: The use of relaxation and guided imagery to reduce stress and improve immune function has great potential benefits for patients with breast cancer. METHODS: This pilot study used a pretest-posttest experimental design with 28 breast cancer patients, aged 25 to 75 years, with the diagnosis of stage 0, 1, or 2 breast cancer. The experimental group received a relaxation and guided imagery intervention and the control group received standard care. The effects of the intervention on immune function were measured by natural killer (NK) cell cytotoxicity and IL-2-activated NK cell activity prior to surgery and 4 weeks postsurgery. NK cell activity was measured using a 15-hr incubation chromium release assay. Cytotoxicity of NK cells was measured against chromium-labeled K-562 target cells. IL-2 was used to enhance reactivity of NK cells against tumor cells. After incubation for 15 hr, cytotoxicity was measured through the release of radioactive chromium. RESULTS: Significant differences between groups were found at 4 weeks postsurgery. T-tests showed increased NK cell cytotoxicity for the intervention group at 100:1, 50:1, and 25:1 effector cell: target cell ratios (E:T) (p < .01 to p < .05) and increased activation for IL-2 at 100:1, 50:1, 25:1, and 12.5:1 (E:T) (p < .01 to p < .05) for the intervention group as compared to the control group. DISCUSSION: These findings suggest that a relaxation intervention such as guided imagery could have an effect on NK cell cytotoxicity and NK cell cytotoxicity after activation with IL-2 in patients undergoing surgery for breast cancer.

Relief of symptoms, side effects, and psychological distress through use of complementary and alternative medicine in women with breast cancer.

PURPOSE/OBJECTIVES: To identify use of complementary and alternative medicine (CAM) for relief of symptoms and side effects among women diagnosed with breast cancer and to identify demographic and clinical factors associated with the use of CAM in these patients. DESIGN: A descriptive, cross-sectional survey. SETTING: Clinics and community groups in the Tampa Bay area and community groups in a rural midwestern area. SAMPLE: A convenience sample of 105 predominantly Caucasian women (mean age = 59 years) with a diagnosis of breast cancer was recruited from the Tampa Bay area and a rural midwestern area. METHODS: The instrument used to gather the data was the Use of Complementary Therapies Survey. The reasons for choosing 33 individual CAM treatments were tabulated. The frequency of use was calculated according to four reasons: (a) to reduce physical symptoms or side effects, (b) to reduce psychological distress, (c) to gain a feeling of control over treatment, or (d) because of dissatisfaction with traditional medical care. Least-squares regression models were fit to identify independent demographic and clinical predictors of CAM therapy use. MAIN RESEARCH VARIABLES: Use of CAM for relief of physical and psychological distress. FINDINGS: Patients used all categories of CAM therapies to reduce physical symptoms and side effects. The most frequently cited reason for use of CAM was to reduce the symptom of psychological distress, whereas the lowest frequency of CAM use was because of dissatisfaction with traditional medical care. Traditional and ethnic medicines frequently were used to reduce physical symptoms and side effects, followed by diet and nutritional supplements. The most frequently used CAM therapy category cited for gaining a feeling of control over treatment was use of diet and nutritional supplements. Previous chemotherapy and having more than a high school education were associated with more frequent use of diet and nutritional supplements and stress-reducing techniques. CONCLUSIONS: Frequency of specific use according to type of CAM was higher and more specific than reported in other studies. Patients who had undergone chemotherapy were most likely to use CAM. IMPLICATIONS FOR NURSING: Oncology nurses are in a key position to identify which symptoms or side effects patients are experiencing and which CAM therapies may be helpful to relieve patients' symptoms related to treatment and psychological distress related to their cancer.

Benign mechanical transport of breast epithelial cells to sentinel lymph nodes.

The evaluation of sentinel lymph nodes (SLNs) for the presence of malignant epithelial cells is essential to the staging of breast cancer patients. Recently, increased attention has focused on the possibility that epithelial cells may reach SLNs by benign mechanical means, rather than by metastasis. The purpose of this study was to test the hypothesis that pre-SLN biopsy breast massage, which we currently use to facilitate the localization of SLNs, might represent a mode of benign mechanical transport. We studied 56 patients with invasive and/or in situ ductal carcinoma and axillary SLNs with only epithelial cells and/or cell clusters (< or =0.2 mm in diameter and not associated with features of established metastases) detected predominantly in subcapsular sinuses of SLNs on hematoxylin and eosin- and/or anti-cytokeratin-stained sections. No patient had an SLN involved by either micro- or macro-metastatic carcinoma. Epithelial cells and cell clusters, < or =0.2 mm in size and without features of established metastases, occurred more frequently in the SLNs of patients who underwent pre-SLN biopsy breast massage (P < 0.001, chi2 test). The latter finding supports the hypothesis that pre-SLN biopsy breast massage is a mode of benign mechanical transport of epithelial cells to SLNs.

Design and testing of the use of a complementary and alternative therapies survey in women with breast cancer.

PURPOSE/OBJECTIVES: To design and test a reliable and valid instrument to determine the frequency of use of complementary and alternative medicine (CAM) therapies among women diagnosed with breast cancer. DESIGN: A descriptive cross-sectional survey. SETTING: Women were recruited from the southeastern area and a rural midwestern area of the United States. SAMPLE: 105 predominantly Caucasian women (mean= 59 years of age) with a diagnosis of breast cancer. METHODS: The Use of Complementary and Alternative Therapies Survey was designed with a content validity index, and reliability was determined with the coefficient alpha. Exploratory factor analysis using a principal components analysis identified primary components (factors) embedded within the survey. Frequency of CAM therapy use was calculated for 33 individual therapies listed on the survey and among three survey-defined subscales of CAM therapies (i.e., diet and nutritional supplements, stress-reducing techniques, and traditional and ethnic medicines). MAIN RESEARCH VARIABLES: Psychometric properties of an instrument to assess frequency of use of CAM among women with breast cancer. FINDINGS: The reported prevalence of use of the individual CAM therapies varied considerably. The coefficient alpha estimate for the total survey was 0.86. Estimates for the individual hypothesized subscales were 0.67 for diet and nutritional supplements, 0.79 for stress-reducing techniques, and 0.80 for traditional and ethnic medicines. The principal components analysis resulted in a two-factor solution with nine items that loaded heavily and uniquely on a factor conceptualized as stress and anxiety reduction and six items that loaded heavily and uniquely on a factor conceptualized as dietary and physical manipulation. The remaining five items (vitamins and minerals, prayer and spiritual healing, massage, reflexology, and aromatherapy) indicated moderate loadings on factors one and two and, thus, were interpreted as equivocal items. CONCLUSIONS: Preliminary data indicated that the instrument is reliable and valid. Additional work is needed to improve the range of items and to test the instrument with other populations. IMPLICATIONS FOR NURSING: Use of CAM by women with breast cancer is believed to be increasing. However, limited data exist on the frequency and predictors of its use in this patient population; therefore, reliable and valid instruments are needed to determine use. If nurses can determine which CAM therapies women are employing, nurses can educate patients with breast cancer on the safe use of these therapies.

Frequency of use of complementary and alternative medicine in women with breast cancer.

PURPOSE/OBJECTIVES: To estimate the frequency of use of complementary and alternative medicine (CAM) therapies among women diagnosed with breast cancer and to identify demographic and clinical factors associated with CAM use in these patients. DESIGN: A descriptive, cross-sectional survey. SAMPLE: A convenience sample of 105 predominantly Caucasian women (mean age = 59 years) with a diagnosis of breast cancer was recruited from the Tampa Bay area and a rural midwestern area. METHODS: Utilizing the "Use of Complementary Therapies Survey," frequency of CAM use was calculated for 33 individual therapies listed on the survey and among three survey-defined subscales of CAM therapies (i.e., diet and nutritional supplements, stress-reducing techniques, and traditional and ethnic medicines). MAIN RESEARCH VARIABLES: Use of CAM therapies and types of treatment in women with breast cancer. FINDINGS: Among diet and nutritional supplements, 64% of all participants reported regular use of vitamins and minerals and 33% regularly used antioxidants, herbs, and health foods. Among stress-reducing techniques, 49% of all participants regularly used prayer and spiritual healing, followed by support groups (37%) and humor or laughter therapy (21%). Traditional and ethnic medicine therapies rarely were used with the exception of massage, which 27% of all participants used at least once after diagnosis. More frequent CAM use was observed among study participants who had undergone previous chemotherapy treatment and those with more than a high school education. Also, being less satisfied with their primary physician was associated with patients' more frequent CAM use. CONCLUSIONS: CAM use is increasing among women with breast cancer, and frequency of specific use according to type of CAM is higher than what has been reported in other studies. Use increased in patients who had undergone chemotherapy and in those with a high school education. IMPLICATIONS FOR NURSING: Oncology nurses are in a key position to identify what treatments patients are using and implement CAM therapies that can be helpful to relieve patient symptoms related to treatment and psychological distress.