Hae-Chung Yang

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.

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.

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.

Sexual Well-Being Among Partnered Women With Breast Cancer Recurrence

PURPOSE A womans risk for sexual disruption after breast cancer recurrence has received little clinical or research attention. PATIENTS AND METHODS Breast cancer patients recently diagnosed with recurrence (n = 60) were initially assessed at baseline and completed follow-ups at 4, 8, and 12 months. They were compared by age, stage, and duration and frequency of follow-up with matched patients who remained disease free (n = 120). Using linear mixed modeling, the groups were compared in their trajectories of change on measures of sexuality, relationship satisfaction, cancer-specific stress, and physical functioning. Recurrence subgroups, those with locoregional versus distant disease and those younger versus older than 52 years, were also compared. RESULTS At baseline, the recurrence group had significantly lower intercourse frequency and physical functioning compared with the disease-free group and these differences were maintained. There were no significant differences in the frequencies of kissing or sexual and relationship satisfactions. For the recurrence group patients, the heightened stress of the diagnostic/early recurrence treatment period declined to the lower disease-free levels by 12 months. This effect was largely due to improvement of the patients with distant disease. Finally, sexual changes were most notable for younger patients. CONCLUSION To our knowledge, this is the first longitudinal, controlled study of sexuality-sexuality in the context of other quality of life domains-for women coping with recurrence. Despite disruption, patients maintained their sexual lives. Younger and distant recurrence patients, however, may have greatest risk of sexual disruption. The factors contributing to sexual disruption remain unknown, and studies investigating strategies to help patients maintain this aspect of quality of life are needed.

Marital quality and survivorship

Although marital distress has been implicated in difficulties with adjustment to a breast cancer diagnosis, its long‐term effects, especially on physical recovery, are unknown.

Marital quality and survivorship: slowed recovery for breast cancer patients in distressed relationships.

Although marital distress has been implicated in difficulties with adjustment to a breast cancer diagnosis, its long‐term effects, especially on physical recovery, are unknown.

Cancer Patients with Major Depressive Disorder: Testing a Biobehavioral/Cognitive Behavior Intervention.

OBJECTIVE In this Phase II trial, we evaluated a novel psychological treatment for depressed patients coping with the stresses of cancer. Effectiveness of a combined biobehavioral intervention (BBI) and cognitive behavior therapy (CBT) was studied. METHOD Participants were 36 cancer survivors (mean age = 49 years; 88% Caucasian; 92% female) diagnosed with major depressive disorder. A single group pre-post design was used. Treatment consisted of up to 20 individual 75-min combined BBI/CBT sessions. Outcomes were change in interviewer (Hamilton Rating Scale for Depression; Williams, 1988) and self-rated depressive symptoms (Beck Depression Inventory-Second Edition; Beck, Steer, & Brown, 1996) as well as change in cancer relevant symptoms (Fatigue Symptom Inventory [Hann et al., 1998] and Brief Pain Questionnaire [Daut, Cleeland, & Flanery, 1983]) and quality of life (Medical Outcomes Study Short Form-36; Ware et al., 1995). Mixed-effects modeling, a reliability change index, and generalized linear models were used. All analyses were intent-to-treat. RESULTS Depressive symptoms significantly improved. In addition, 19 of 21 study completers met criteria for remission. Significant improvements were also noted in fatigue and mental health quality of life. Both concurrent anxiety disorders and high levels of cancer stress (Impact of Events Scale; Horowitz, Wilner, & Alvarez, 1979) were each associated with beginning and concluding treatment with greater depressive symptoms. CONCLUSIONS CBT components were successfully incorporated into a previously efficacious intervention for reducing cancer stress. The BBI/CBT intervention warrants further research in evaluating its efficacy compared with well-established treatments for depression.

Association of the physiological stress response with depressive symptoms in patients with breast cancer.

Objective The literature on the relationship of depressive symptoms and stress hormones after cancer diagnosis has been mixed, with some studies showing a relationship and other studies showing none. Time since diagnosis may explain these contradictory findings. This study examined the relationship of depressive symptoms to stress hormones in patients with breast cancer using 12-month longitudinal data. Methods Patients with Stage II or III breast cancer (n = 227) were assessed every 4 months from diagnosis/surgery to 12 months. They completed the Centers for Epidemiological Studies Depression Scale (CES-D) Iowa Short Form and the Perceived Stress Scale and blood samples were obtained to measure stress hormones (i.e., cortisol, adrenocorticotropin hormone, norepinephrine, and epinephrine). Results Depressive symptoms were negatively related to cortisol levels (&bgr;= −0.023, p = .002) but were positively related to rate of change in cortisol (&bgr; = 0.003, p = .003). Adrenocorticotropin hormone, epinephrine, and norepinephrine did not covary with depressive symptoms (all p values > .05). When the CES-D and Perceived Stress Scale were both used to predict cortisol, only the CES-D was significantly related (&bgr; = −0.025, p = .017). Conclusions Depressive symptoms were negatively related to cortisol, but this relationship changed from the time of diagnosis/surgery through 12 months. Cortisol may initially provide a buffering effect against depression during the stress of initial diagnosis and treatment, but this relationship seems to change over time.

Marital quality and survivorship: Slowed recovery for breast cancer patients in distressed relationships (Original Article)

Although marital distress has been implicated in difficulties with adjustment to a breast cancer diagnosis, its long‐term effects, especially on physical recovery, are unknown.