Jeanne Walter

Cytokine Comparisons Between Women With Breast Cancer and Women With a Negative Breast Biopsy

Background: Understanding the biological milieu associated with disease states has important implications for biobehavioral research. Cytokines, signaling molecules that mediate and regulate immunity, inflammation, and hematopoiesis, are an important component of the biological milieu associated with breast cancer. Cytokines have been used as biomarkers in research for prognosis and have been associated with symptoms and adverse outcomes in multiple conditions, including breast cancer. To date, however, the examination of cytokine patterns has been limited by traditional laboratory methods. Advances in proteomic technology now permit the characterization of a broader array of cytokines in a single specimen. Because cytokines operate in integrated networks, a more complete understanding will be gained as multiple cytokines can be examined for patterns of response that may be associated with symptoms and prognosis. Objectives: To use proteomic technology (a) to examine whether there was a difference in cytokine levels and patterns in women with breast cancer compared with controls, (b) to define and compare the receiver operator characteristic curves for standard cytokine classifications, and (c) to identify the best-fitting empirical model of cytokines to distinguish groups of women found to have breast cancer from those with negative biopsies. Methods: The cytokine levels of 35 women who had been diagnosed recently with breast cancer were compared with 24 women with a suspicious breast mass who were found subsequently to have a negative breast biopsy. Multiplex bead array assays permitted the simultaneous measure of multiple markers in a small volume of serum. Nonparametric procedures were used to determine differences in the median values and the distributions for each cytokine. The receiver operator characteristic curves were defined to identify patterns of cytokines. Results: There were significantly higher systemic cytokine values in women with cancer in comparison with those in women without cancer for all cytokines measured, with the exception of granulocyte colony-stimulating factor and interferon-gamma. The only significant associations found between cytokines and age or race were increased levels of interleukin-8 (r = .53) and macrophage inflammatory protein-1&bgr; (r = .45) with increased age in women with a negative biopsy. Three cytokines (granulocyte colony-stimulating factor, interleukin-6, and interleukin-17) distinguished between the breast cancer and no-cancer groups with an exceptionally high areas under the curve (0.981; SE = 0.017). Discussion: Levels of cytokines and their patterns were markedly different in women with breast cancer as compared with those in women who did not have breast cancer. Results from this study highlight the need for further research to examine the levels and patterns of cytokines that may serve as biomarkers in clinical research. Innovations in proteomic technology have implications for expanding biobehavioral research.

A randomized clinical trial of alternative stress management interventions in persons with HIV infection.

Research in psychoneuroimmunology suggests that immunosuppression associated with perceived stress may contribute to disease progression in persons with HIV infection. While stress management interventions may enhance immune function, few alternative approaches have yet been tested. This randomized clinical trial was conducted to test effects of three 10-week stress management approaches--cognitive-behavioral relaxation training (RLXN), focused tai chi training (TCHI), and spiritual growth groups (SPRT)--in comparison to a wait-listed control group (CTRL) among 252 individuals with HIV infection. Using repeated measures mixed modeling, the authors found that in comparison to the CTRL group, (a) both the RLXN and TCHI groups used less emotion-focused coping, and (b) all treatment groups had augmented lymphocyte proliferative function. Despite modest effects of the interventions on psychosocial functioning, robust findings of improved immune function have important clinical implications, particularly for persons with immune-mediated illnesses.

Implementing a comprehensive approach to the study of health dynamics using the psychoneuroimmunology paradigm.

This article addresses psychoneuroimmunology (PNI) as an integrative paradigm for advancing both theoretical and empirical knowledge of physiological patterns that contribute to the dynamics of health. We depict relationships among relevant psychobehavioral and physiological components in a PNI-based framework. We then provide examples of how this framework guided 2 clinical trials designed to assess the effectiveness of selected nursing interventions to reduce stress and enhance coping, one in persons with human immunodeficiency viral disease and the other in persons with cancer. The examples address disease-specific measures for assessing the components of the PNI-based framework.

Tryptophan degradation in women with breast cancer: a pilot study

BackgroundAltered tryptophan metabolism and indoleamine 2,3-dioxygenase activity are linked to cancer development and progression. In addition, these biological factors have been associated with the development and severity of neuropsychiatric syndromes, including major depressive disorder. However, this biological mechanism associated with both poor disease outcomes and adverse neuropsychiatric symptoms has received little attention in women with breast cancer. Therefore, a pilot study was undertaken to compare levels of tryptophan and other proteins involved in tryptophan degradation in women with breast cancer to women without cancer, and secondarily, to examine levels in women with breast caner over the course of chemotherapy.FindingsBlood samples were collected from women with a recent diagnosis of breast cancer (n = 33) before their first cycle of chemotherapy and after their last cycle of chemotherapy. The comparison group (n = 24) provided a blood sample prior to breast biopsy. Plasma concentrations of tryptophan, kynurenine, and tyrosine were determined. The kynurenine to tryptophan ratio (KYN/TRP) was used to estimate indoleamine 2,3-dioxygenase activity. On average, the women with breast cancer had lower levels of tryptophan, elevated levels of kynurenine and tyrosine and an increased KYN/TRP ratio compared to women without breast cancer. There was a statistically significant difference between the two groups in the KYN/TRP ratio (p = 0.036), which remained elevated in women with breast cancer throughout the treatment trajectory.ConclusionsThe findings of this pilot study suggest that increased tryptophan degradation may occur in women with early-stage breast cancer. Given the multifactorial consequences of increased tryptophan degradation in cancer outcomes and neuropsychiatric symptom manifestation, this biological mechanism deserves broader attention in women with breast cancer.

Psychoneuroimmunology-Based Stress Management during Adjuvant Chemotherapy for Early Breast Cancer

Objective. In a randomized trial of women with early stage breast cancer undergoing adjuvant chemotherapy, two stress management interventions, tai chi training and spiritual growth groups, were compared to a usual care control group, to evaluate psychosocial functioning, quality of life (QOL), and biological markers thought to reflect cancer- and treatment-specific mechanisms. Method. The sample consisted of 145 women aged 27–75 years; 75% were Caucasian and 25% African American. A total of 109 participants completed the study, yielding a 75% retention rate. Grounded in a psychoneuroimmunology framework, the overarching hypothesis was that both interventions would reduce perceived stress, enhance QOL and psychosocial functioning, normalize levels of stress-related neuroendocrine mediators, and attenuate immunosuppression. Results. While interesting patterns were seen across the sample and over time, the interventions had no appreciable effects when delivered during the period of chemotherapy. Conclusions. Findings highlight the complex nature of biobehavioral interventions in relation to treatment trajectories and potential outcomes. Psychosocial interventions like these may lack sufficient power to overcome the psychosocial or physiological stress experienced during the chemotherapy treatment period. It may be that interventions requiring less activity and/or group attendance would have enhanced therapeutic effects, and more active interventions need to be tested prior to and following recovery from chemotherapy.

Psychometric Evaluation of the Patient-Reported Outcomes Measurement Information System Fatigue-Short Form Across Diverse Populations.

Background The need for reliable, valid tools to measure patient-reported outcomes (PROs) is critical both for research and for evaluating treatment effects in practice. The Patient-Reported Outcomes Measurement Information System Fatigue-Short Form v1.0-Fatigue 7a (PROMIS F-SF) has had limited psychometric evaluation in various populations. Objectives The aim of the study is to examine psychometric properties of PROMIS F-SF item responses across various populations. Methods Data from five studies with common data elements were used in this secondary analysis. Samples from patients with fibromyalgia, sickle cell disease, cardiometabolic risk, pregnancy, and healthy controls were used. Reliability was estimated using Cronbach’s alpha. Dimensionality was evaluated with confirmatory factor analysis. Concurrent validity was evaluated by examining Pearson’s correlations between scores from the PROMIS F-SF, the Multidimensional Fatigue Symptom Inventory-Short Form, and the Brief Fatigue Inventory. Discriminant validity was evaluated by examining Pearson’s correlations between scores on the PROMIS F-SF and measures of stress and depressive symptoms. Known groups validity was assessed by comparing PROMIS F-SF scores in the clinical samples to healthy controls. Results Reliability of PROMIS F-SF scores was adequate across samples, ranging from .72 in the pregnancy sample to .88 in healthy controls. Unidimensionality was supported in each sample. Concurrent validity was strong; across the groups, correlations with scores on the Multidimensional Fatigue Symptom Inventory-Short Form and Brief Fatigue Inventory ranged from .60 to .85. Correlations of the PROMIS F-SF with measures of stress and depressive mood were moderate to strong, ranging from .37 to .64. PROMIS F-SF scores were significantly higher in clinical samples compared to healthy controls. Discussion Reliability and validity of the PROMIS F-SF were acceptable. The PROMIS F-SF is a suitable measure of fatigue across the four diverse clinical populations included in the analysis.

Tai chi as a biobehavioral intervention for women with breast cancer

Paroxetine for the prevention of depression in patients undergoing treatment with interferon-a plus ribavirin for hepatitis C Charles L. Raison , Bobbi J. Woolwine , Jose Binongo , Jeffrey Staub , Robert Weinreib , Robin Rosenblate , Dwight L. Evans , Gregory M. Asnis , Andrew H. Miller a a Emory University School of Medicine, USA b University of Pennsylvania, USA c Rush University Medical Center, USA d Albert Einstein College of Medicine, USA

Challenges in Interpreting Cytokine Biomarkers in Biobehavioral Research: A Breast Cancer Exemplar

Purpose: This report extends the findings of a prior study comparing the level of plasma cytokines in women with breast cancer to those of women with a benign breast biopsy with the addition of a normal comparison group. The results of this three-group comparison are presented as background for discussing several methodologic challenges for biobehavioral research in inflammatory-based conditions. Method: This study used a descriptive, cross-sectional design to compare the levels of plasma cytokines in women with breast cancer, women with a benign breast biopsy, and a normal comparison group. The levels of 17 cytokines were measured using multiplex bead array assays (Bio-Plex®). Data analysis included a variety of descriptive and graphical techniques to illustrate between-group differences in cytokine profiles. Results: The levels of plasma cytokines in the sample of 35 women who had recently been diagnosed with breast cancer, 24 women with a suspicious breast mass, who subsequently were found to have a benign breast biopsy, and 33 women in a normal comparison group present a background for discussing the implications of extreme between-group differences for biobehavioral nursing research. Both the levels of individual cytokines and their patterns were distinctly different in the three groups. Conclusion: The exemplar presented from the three-group comparison has implications for planning biobehavioral nursing research in patients with conditions characterized by inflammation.

#97 Tai Chi training enhances well-being and alters cytokine levels in persons with HIV disease ☆

of confounding factors, including the patient s medical condition. Thus, the goal of the present study was to examine whether a relatively stable marker of chronic inflammation, circulating levels of interleukin 6 (IL-6), was associated with cognitive function in a community sample of 480 healthy adults aged 30–54 years (mean = 45). Participants (228 male; 81.5% Caucasian, 18.5% African-American) were enrolled in the Adult Health and Behavior (AHAB) project, an ongoing study of cardiovascular risk. All participants completed a battery of neuropsychological tests. After controlling for age, sex, race, current smoking, and years of education, levels of circulating IL-6 were inversely associated with short-term spatial memory and flexibility (Wechsler Memory Scale (WMS): Spatial Span, p < .02), delayed verbal memory (WMS: Logical Memory, p < .02), executive functioning (Stroop task, p < .02). There was no association between IL-6 level and verbal learning or short-term verbal memory (WMS ñ Logical Memory (Immediate Recall) or Verbal Paired Associates tasks) or selective attention (Digit Vigilance Task). These data provide initial evidence that cytokine-mediated inflammatory processes are associated with a decline in spatial memory, learning, and cognition in humans that is consistent with the animal literature. This raises the possibility that increases in circulating levels of IL-6 with advancing age play a role in cognitive decline.