Lisa M. Thornton

Psychologic Intervention Improves Survival for Breast Cancer Patients A Randomized Clinical Trial

The question of whether stress poses a risk for cancer progression has been difficult to answer. A randomized clinical trial tested the hypothesis that cancer patients coping with their recent diagnosis but receiving a psychologic intervention would have improved survival compared with patients who were only assessed.

Traumatic Stress, Perceived Global Stress, and Life Events: Prospectively Predicting Quality of Life in Breast Cancer Patients.

The authors investigated the relationship between stress at initial cancer diagnosis and treatment and subsequent quality of life (QoL). Women (n = 112) randomized to the assessment-only arm of a clinical trial were initially assessed after breast cancer diagnosis and surgery and then reassessed at 4 months (during adjuvant treatment) and 12 months (postadjuvant treatment). There were 3 types of stress measured: number of stressful life events (K. A. Matthews et al., 1997), cancer-related traumatic stress symptoms (M. J. Horowitz, N. Wilner, & W. Alvarez, 1979), and perceived global stress (S. Cohen, T. Kamarck, & R. Mermelstein, 1983). Using hierarchical multiple regressions, the authors found that stress predicted both psychological and physical QoL (J. E. Ware, K. K. Snow, & M. Kosinski, 2000) at the follow-ups (all ps < .03). These findings substantiate the relationship between initial stress and later QoL and underscore the need for timely psychological intervention.

The Pain, Depression, and Fatigue Symptom Cluster in Advanced Breast Cancer: Covariation with the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system

OBJECTIVE Neuroendocrine-immune models have been proposed to account for the frequent co-occurrence of pain, depression, and fatigue (PDF) among cancer patients. DESIGN In a cross-sectional observational study of advanced cancer patients (N = 104), we tested the hypothesis that the PDF cluster covaries with proposed biological mediators: hormones of the sympathetic nervous system (SNS) and the hypothalamic-pituitary-adrenal (HPA) axis. MAIN OUTCOME MEASURES PDF symptoms were measured using the Brief Pain Inventory, Fatigue Symptom Inventory, and the Center for Epidemiological Studies Depression scales. HPA activation was indicated by plasma levels of cortisol and adrenocorticotropic hormone, and SNS activation was indicated by plasma epinephrine and norepinephrine. RESULTS Preliminary analyses supported the use of covariance structure modeling to test whether shared variance among hormone levels predicted shared variance among PDF symptoms. Latent variable analysis indicated that neuroendocrine levels predicted PDF (standardized beta = .23, p = .039), while controlling for important disease and demographic variables. CONCLUSION Previous studies have linked individual symptoms to individual biomarkers. The observed significant paring of the 4 hormones to the PDF cluster provides the first evidence suggestive of stress hormones as a common mechanism for the co-occurrence of pain, depression, and fatigue symptoms.

Biobehavioral, immune, and health benefits following recurrence for psychological intervention participants.

Purpose: A clinical trial was designed to test the hypothesis that a psychological intervention could reduce the risk of cancer recurrence. Newly diagnosed regional breast cancer patients (n = 227) were randomized to the intervention-with-assessment or the assessment-only arm. The intervention had positive psychological, social, immune, and health benefits, and after a median of 11 years the intervention arm was found to have reduced the risk of recurrence (hazard ratio, 0.55; P = 0.034). In follow-up, we hypothesized that the intervention arm might also show longer survival after recurrence. If observed, we then would examine potential biobehavioral mechanisms. Experimental Design: All patients were followed; 62 recurred. Survival analyses included all 62. Upon recurrence diagnosis, those available for further biobehavioral study were accrued (n = 41, 23 intervention and 18 assessment). For those 41, psychological, social, adherence, health, and immune (natural killer cell cytotoxicity, T-cell proliferation) data were collected at recurrence diagnosis and 4, 8, and 12 months later. Results: Intent-to-treat analysis revealed reduced risk of death following recurrence for the intervention arm (hazard ratio, 0.41; P = 0.014). Mixed-effects follow-up analyses with biobehavioral data showed that all patients responded with significant psychological distress at recurrence diagnosis, but thereafter only the intervention arm improved (P values < 0.023). Immune indices were significantly higher for the intervention arm at 12 months (P values < 0.017). Conclusions: Hazards analyses augment previous findings in showing improved survival for the intervention arm after recurrence. Follow-up analyses showing biobehavioral advantages for the intervention arm contribute to our understanding of how improved survival was achieved. Clin Cancer Res; 16(12); 3270–8. ©2010 AACR.

A Psychological Intervention Reduces Inflammatory Markers by Alleviating Depressive Symptoms: Secondary Analysis of a Randomized Controlled Trial

Objectives: To test experimentally whether a psychological intervention reduces depression-related symptoms and markers of inflammation among cancer patients and to test one mechanism for the intervention effects. Depression and inflammation are common among cancer patients. Data suggest that inflammation can contribute to depressive symptoms, although the converse remains untested. Methods: As part of a randomized clinical trial, newly diagnosed breast cancer patients (n = 45) with clinically significant depressive symptoms were evaluated and randomized to psychological intervention with assessment or assessment only study arms. The intervention spanned 12 months, with assessments at baseline, 4, 8, and 12 months. Mixed-effects modeling tested the hypothesis that the intervention reduced self-reported depressive symptoms (Center for Epidemiological Studies Depression scale, Profile of Mood States Depression and Fatigue subscales, and Medical Outcomes Study-Short Form 36 Bodily Pain subscale) and immune cell numbers that are elevated in the presence of inflammation (white blood cell count, neutrophil count, and helper/suppressor ratio). Mediation analyses tested whether change in depressive symptoms, pain, or fatigue predicted change in white blood cell count, neutrophil count, or the helper/suppressor ratio. Results: The intervention reduced significantly depressive symptoms, pain, fatigue, and inflammation markers. Moreover, the intervention effect on inflammation was mediated by its effect on depressive symptoms. Conclusions: This is the first experiment to test whether psychological treatment effective in reducing depressive symptoms would also reduce indicators of inflammation. Data show that the intervention reduced directly depressive symptoms and reduced indirectly inflammation. Psychological treatment may treat effectively depressive symptoms, pain, and fatigue among cancer patients. CES-D = Center for Epidemiological Studies-Depression scale, Iowa short form; SF-36 = Medical Outcomes Study-Short Form 36; KPS = Karnofsky Performance Status.

Cellular Immunity in Breast Cancer Patients Completing Taxane Treatment

Purpose: A field study of postchemotherapy immune functioning relative to the use of taxanes is reported. Immune responses in breast cancer patients were analyzed as a function of whether patients received taxane as part of their adjuvant chemotherapy. Experimental Design: Immune levels of 227 stage II/III breast cancer patients were measured immediately after surgery prior to chemotherapy and again 12 months later when all chemotherapies had been completed. T-cell blastogenesis and natural killer (NK) cell lysis levels of patients receiving taxanes (n = 55) were compared with levels of patients not receiving taxanes (n = 172). Results: Regression analyses were conducted. The administration of taxane as part of combination chemotherapy predicted increased T-cell blastogenesis and NK cell cytotoxicity after the conclusion of all chemotherapies. For the Taxane group, average phytohemagglutinin-induced blastogenesis was 37% higher and NK cell cytotoxicity was 39% higher than the values for the No-Taxane group. Conclusions: Data from group comparisons with appropriate controls in a sizable clinical sample contravene traditional wisdom that taxanes suppress patients’ immune cell functions. Problems in generalizing direct-contact laboratory models to the field of cancer treatment are highlighted.

Psychological stress is associated with altered levels of myeloid-derived suppressor cells in breast cancer patients.

Our group has shown in a randomized clinical trial that psychological intervention to reduce stress in patients with stages II and III breast cancer led to enhanced immune function, fewer recurrences and improved overall survival. We hypothesized that patients with high levels of stress would have alterations in myeloid-derived suppressor cells (MDSC) compared to patients with lower stress. PBMC from 16 patients with high stress (n = 8) or with low stress (n = 8) after surgery as measured by the Impact of Event Scale (IES) questionnaire were evaluated for the presence of MDSC. Patients with higher IES scores had significantly elevated salivary cortisol levels (P = 0.013; 13 μg/dl vs. 9.74 μg/dl). Levels of IL-1Rα were also significantly elevated in the higher IES group (45.09 pg/ml vs. 97.16 pg/ml; P = 0.010). IP 10, G-CSF, and IL-6 were all higher in the high stress group although not to a significant degree. Flow cytometric analysis for CD33+/HLA-DR-neg/CD15+/CD11b+ MDSC revealed increased MDSC in patients with lower IES scores (P = 0.009). CD11b+/CD15+ cells constituted 9.4% of the CD33+/HLA DR-neg cell population in patients with high IES, vs. 27.3% in patients with low IES scores. Additional analyzes of the number of stressful events that affected the patients in addition to their cancer diagnosis revealed that this type of stress measure correlated with elevated levels of MDSC (P = 0.064). These data indicate the existence of a complex relationship between stress and immune function in breast cancer patients.

Delayed Emotional Recovery After Taxane-based Chemotherapy

There are few patient‐reported data regarding quality of life after taxane‐based adjuvant chemotherapy and none regarding mental health outcomes.

Test of mindfulness and hope components in a psychological intervention for women with cancer recurrence.

OBJECTIVE Psychological interventions can attenuate distress and enhance coping for those with an initial diagnosis of cancer, but there are few intervention options for individuals with cancer recurrence. To address this gap, we developed and tested a novel treatment combining Mindfulness, Hope Therapy, and biobehavioral components. METHOD An uncontrolled, repeated measures design was used. Women (N = 32) with recurrent breast or gynecologic cancers were provided 20 treatment sessions in individual (n = 12) or group (n = 20) formats. On average, participants were middle aged (M = 58) and Caucasian (81%). Independent variables (i.e., hope and mindfulness) and psychological outcomes (i.e., depression, negative mood, worry, and symptoms of generalized anxiety disorder) were assessed pre-treatment and 2, 4, and 7 months later. Session-by-session therapy process (positive and negative affect, quality-of-life) and mechanism (use of intervention-specific skills) measures were also included. RESULTS Distress, anxiety, and negative affect decreased, whereas positive affect and mental-health-related quality-of-life increased over the course of treatment, as demonstrated in mixed-effects models with the intent-to-treat sample. Both hope and mindfulness increased, and use of mindfulness skills was related to decreased anxiety. CONCLUSIONS This treatment was feasible to deliver and was acceptable to patients. The trial serves as preliminary evidence for a multi-component intervention tailored to treat difficulties specific to recurrent cancer. The blending of the components was novel as well as theoretically and practically consistent. A gap in the literature is addressed, providing directions for testing interventions designed for patients coping with the continuing stressors and challenges of cancer recurrence.

Cardiovascular Stress Responses Among Asian Indian and European American Women and Men

Asian Indians have approximately 3 times the rate of coronary artery disease as do age-matched European Americans, but the increased risk cannot be explained by the presence of known physiological and behavioral risk factors. One previous study suggested that Asian Indians have diminished vasoactive responses to isoproterenol, but no published study has examined responses to psychological stressors. The purpose of this study was to test the hypothesis that the vasomotor response to stress, as indexed by hemodynamic measures, would be exaggerated in Asian Indian men and women, relative to European American individuals. Thirty-seven Asian Indian and 43 European American men and women were tested in a standard reactivity protocol, whereas heart rate, blood pressure, and cardiac impedance measures were assessed. Asian Indian men and women had significantly smaller changes in systolic blood pressure and mean arterial pressure during the stressors, relative to European American men and women. Asian Indian women, but not men, had significantly smaller diastolic blood pressure and total peripheral-resistance index changes to the stressors, relative to the other 3 groups. These data are in contrast to our expectation of decreased tendency of Asian Indians to vasodilate during psychological stress but do suggest that sex and Asian Indian ethnicity interact to influence vascular reactivity to stressors.