Center on Stress and Health

Cancer, and Stress and Trauma

Palesh, O. G., K. Collie, D. Batiuchok, J. Tilston, C. Koopman, M. L. Perlis, L. D. Butler, R. Carlson and D. Spiegel (2007). "A longitudinal study of depression, pain, and stress as predictors of sleep disturbance among women with metastatic breast cancer." Biol Psychol 75(1): 37-44.
OBJECTIVE: Sleep disturbances are common among women with breast cancer and can have serious consequences. The present study examined depression, pain, life stress, and participation in group therapy in relation to sleep disturbances in a sample of women with metastatic breast cancer. METHODS: Ninety-three women with metastatic breast cancer participated in a large intervention trial examining the effect of the group therapy on their symptoms. They completed measures of depression, pain, life stress, and sleep disturbance at baseline, 4, 8 and 12 months. RESULTS: The results showed that higher initial levels of depression at baseline predicted problems associated with getting up in the morning, waking up during the night, and daytime sleepiness. Increases in depression over the course of 12 months were associated with fewer hours of sleep, more problems with waking up during the night and more daytime sleepiness. Higher levels of pain at baseline predicted more problems getting to sleep. Increases in pain predicted more difficulty getting to sleep and more problems waking up during the night. Greater life stress at baseline predicted more problems getting to sleep and more daytime sleepiness. CONCLUSIONS: Depression, pain, and life stress scores were each associated with different types of negative change in self-reported sleep disturbances. Depression, especially worsening depression, was associated with the greatest number of types of negative change. The relationships found between sleep disturbance and depression, pain, and life stress suggest specific ways to address the problem of sleep disturbance for women with metastatic breast cancer and show how different types of disturbed sleep may be clinical markers for depression, pain, or life stress in this population.

Wong, M., E. Looney, J. Michaels, O. Palesh and C. Koopman (2006). "A preliminary study of peritraumatic dissociation, social support, and coping in relation to posttraumatic stress symptoms for a parent's cancer." Psychooncology 15(12): 1093-8.
This study examined predictors of posttraumatic stress disorder (PTSD) symptoms in adults who, as children, had a parent diagnosed with cancer. Possible predictors of adulthood PTSD examined were peritraumatic dissociation, satisfaction with social support, coping through denial, behavioral disengagement and self-distraction, and whether or not the parent died. Thirty research participants (20 women and 10 men, ages 18-38) were recruited who were 8-17-years old at the time of a parent's cancer diagnosis. Each participant completed measures of their current PTSD symptoms in response to their parent's cancer, peritraumatic dissociative experiences, demographic characteristics, and satisfaction with social support and use of coping strategies at the time of their parent's cancer diagnosis. Seventeen percent met screening criteria for likely PTSD. As hypothesized, PTSD symptoms were strongly and positively correlated with peritraumatic dissociation. Furthermore, PTSD symptoms were greater among females and were related to greater use of denial and behavioral disengagement and to less satisfaction with social support. These results suggest that health care providers need to recognize symptoms of peritraumatic dissociation in the children of parents who are diagnosed with cancer so that steps can be taken to minimize the children's development of PTSD that may extend into their adult lives.

Spiegel, D., J. Giese-Davis, C. B. Taylor and H. Kraemer (2006). "Stress sensitivity in metastatic breast cancer: analysis of hypothalamic-pituitary-adrenal axis function." Psychoneuroendocrinology 31(10): 1231-44.
The normal diurnal cortisol cycle has a peak in the morning, decreasing rapidly over the day, with low levels during the night, then rising rapidly again to the morning peak. A pattern of flatter daytime slopes has been associated with more rapid cancer progression in both animals and humans. We studied the relationship between the daytime slopes and other daytime cortisol responses to both pharmacological and psychosocial challenges of hypothalamic-pituitary-adrenal (HPA) axis function as well as DHEA in a sample of 99 women with metastatic breast cancer, in hopes of elucidating the dysregulatory process. We found that the different components of HPA regulation: the daytime cortisol slope, the rise in cortisol from waking to 30 min later, and cortisol response to various challenges, including dexamethasone (DEX) suppression, corticotrophin releasing factor (CRF) activation, and the Trier Social Stress Task, were at best modestly associated. Escape from suppression stimulated by 1mg of DEX administered the night before was moderately but significantly associated with flatter daytime cortisol slopes (r=0.28 to .30 at different times of the post DEX administration day, all p<.01). Daytime cortisol slopes were also moderately but significant associated with the rise in cortisol from waking to 30 min after awakening (r=.29, p=.004, N=96), but not with waking cortisol level (r=-0.13, p=.19). However, we could not detect any association between daytime cortisol slope and activation of cortisol secretion by either CRF infusion or the Trier Social Stress Task. The CRF activation test (following 1.5mg of DEX to assure that the effect was due to exogenous CRF) produced ACTH levels that were correlated (r=0.66, p<.0001, N=74) with serum cortisol levels, indicating adrenal responsiveness to ACTH stimulation. Daytime cortisol slopes were significantly correlated with the slope of DHEA (r=.21, p=.04, N=95). Our general findings suggest that flatter daytime cortisol slopes among metastatic breast cancer patients may be related to disrupted feedback inhibition rather than hypersensitivity in response to stimulation.

Palesh, O. G., T. Shaffer, J. Larson, S. Edsall, X. H. Chen, C. Koopman, J. M. Turner-Cobb, M. A. Kreshka, K. Graddy and R. Parsons (2006). "Emotional self-efficacy, stressful life events, and satisfaction with social support in relation to mood disturbance among women living with breast cancer in rural communities." Breast J 12(2): 123-9.
This study evaluated the relationships of emotional self-efficacy, stressful life events, and social support with mood disturbance among women diagnosed with breast cancer who live in rural communities. Eighty-two women completed measures of demographic characteristics, medical status, and psychosocial variables. Using multiple regression analysis, we found that greater mood disturbance was related to having less emotional self-efficacy (p < 0.001) and to having experienced more stressful life events (p = 0.02), while satisfaction with social support was not significantly related to mood disturbance (adjusted R2 = 0.39). Women living with breast cancer in rural communities who have experienced multiple stressful life events may have an increased risk for mood disturbance, whereas having greater emotional self-efficacy may provide resilience against mood disturbance.

Giese-Davis, J., F. H. Wilhelm, A. Conrad, H. C. Abercrombie, S. Sephton, M. Yutsis, E. Neri, C. B. Taylor, H. C. Kraemer and D. Spiegel (2006). "Depression and stress reactivity in metastatic breast cancer." Psychosom Med 68(5): 675-83.
OBJECTIVE: Cancer-related distress due to the psychological and physical challenges of metastatic breast cancer (MBC) may result in symptoms of depression, which negatively affects quality and may influence quantity of life. This study investigated how depression affects MBC stress reactivity, including autonomic (ANS) and hypothalamic-pituitary-adrenal (HPA) axis function. METHOD: Forty-five nondepressed and 45 depressed patients with MBC underwent a modified Trier Social Stress Test (TSST) while affect, cardiovascular, respiratory, and cortisol responses were measured. RESULTS: At study entry, depressed compared with nondepressed patients had significantly lower log cortisol waking rise levels (p = .005) but no other HPA differences. Positive affect (p = .025) and high-frequency heart-rate variability (lnHF) (p = .002) were significantly lower at TSST baseline in depressed patients. In response to the TSST, depressed patients reported significantly lower positive (p = .050) and greater negative affect (p = .037) and had significantly reduced lnHF (p = .031). In secondary analyses, at TSST baseline both low-frequency (lnLF) (p = .002) and very-low-frequency (lnVLF) (p = .0001) heart rate variability were significantly lower in the depressed group. In secondary analyses during the TSST, those who were depressed had significantly lower lnVLF (p = .008) and did not increase aortic impedance reactivity as much as did the nondepressed during the stressor (p = .005). CONCLUSION: Depression in patients with MBC was associated with alterations in autonomic regulation, particularly reductions in respiratory sinus arrhythmia, a measure of cardiac vagal control, at baseline and during the TSST. In addition, depression was associated with blunted HPA response to awakening. Both MBC groups had relative cortisol hyporesponsiveness to acute stress.

Giese-Davis, J., C. Bliss-Isberg, K. Carson, P. Star, J. Donaghy, M. J. Cordova, N. Stevens, L. Wittenberg, C. Batten and D. Spiegel (2006). "The effect of peer counseling on quality of life following diagnosis of breast cancer: an observational study." Psychooncology 15(11): 1014-22.
Women with breast cancer express the greatest need for counseling at the time of diagnosis and report that the intervention they want is to be able to speak with someone who has the same cancer, but has lived through the crisis of treatment and is leading a 'normal' life. We conducted an observational study of a 6-month peer-counseling intervention testing outcomes for both newly diagnosed women (Sojourners) and peer counselors (Navigators) as a first step toward the goal of validating a peer navigator program. Significant improvement in the Sojourners was observed in trauma symptoms, emotional well-being, cancer self-efficacy, and desire for information on breast cancer resources. Navigators maintained baseline levels of the outcome variables, but increased in dissatisfaction with their interactions with their medical team and increased emotional suppression. Our findings indicate that peer navigation may halt a decline in quality of life that is commonly found in the first year following breast cancer diagnosis. In addition, Navigators were not adversely affected by their experience; however, careful training and supervision of Navigators is crucial to overall success. Randomized clinical trials are needed to demonstrate the efficacy of peer navigator programs.

Han, W. T., K. Collie, C. Koopman, J. Azarow, C. Classen, G. R. Morrow, B. Michel, E. Brennan-O'Neill and D. Spiegel (2005). "Breast cancer and problems with medical interactions: relationships with traumatic stress, emotional self-efficacy, and social support." Psychooncology 14(4): 318-30.
This investigation examined relationships between breast cancer patients' psychosocial characteristics (impact of the illness, traumatic stress symptoms, emotional self-efficacy, and social support) and problems they perceived in their medical interactions and their satisfaction with their physicians. Participants were 352 women enrolled in a multicenter trial of the effects of group therapy for women with recently diagnosed primary breast cancer. The findings reported here are from a cross-sectional analysis of baseline data gathered prior to randomization. Problems interacting with physicians and nurses were associated with greater levels of cancer-related traumatic stress (p < 0.01), less emotional self-efficacy for cancer (p < 0.05), less satisfaction with informational support from family, friends, and spouse, and a tendency to perceive those sources of support as more aversive (p < 0.05). Women who were less satisfied with emotional support from their family, friends and spouse were less likely to feel satisfied with their physicians (p < 0.05). These patient characteristics identify women with primary breast cancer who are likely to experience difficulty in their interactions with nurses and physicians and to be less satisfied with their physicians.

Butler, L. D., N. P. Field, A. L. Busch, J. E. Seplaki, T. A. Hastings and D. Spiegel (2005). "Anticipating loss and other temporal stressors predict traumatic stress symptoms among partners of metastatic/recurrent breast cancer patients." Psychooncology 14(6): 492-502.
This study examined pre- and post-loss levels of posttraumatic stress symptoms (intrusion and avoidance) in partners of metastatic/recurrent breast cancer patients, and the relationship of these symptoms to past, current, and anticipatory stressors. The results indicate that 34% (17/50) of the partners experienced clinically significant symptom levels prior to the patients' deaths. Prior to loss, partners' symptoms were positively associated with their current level of perceived stress and anticipated impact of the loss; whereas following loss, partners' symptoms were predicted by higher pre-loss levels of symptoms, past family deaths, and anticipated impact of the loss. Limitations and treatment implications of the present research and directions for future research are discussed.

Abercrombie, H. C., J. Giese-Davis, S. Sephton, E. S. Epel, J. M. Turner-Cobb and D. Spiegel (2004). "Flattened cortisol rhythms in metastatic breast cancer patients." Psychoneuroendocrinology 29(8): 1082-92.
Allostatic load, the physiological accumulation of the effects of chronic stressors, has been associated with multiple adverse health outcomes. Flattened diurnal cortisol rhythmicity is one of the prototypes of allostatic load, and has been shown to predict shorter survival among women with metastatic breast cancer. The current study compared diurnal cortisol slope in 17 breast cancer patients and 31 controls, and tested associations with variables previously found to be related to cortisol regulation, i.e, abdominal adiposity, perceived stress, social support, and explicit memory. Women with metastatic breast cancer had significantly flatter diurnal cortisol rhythms than did healthy controls. Patients with greater disease severity showed higher mean cortisol levels, smaller waist circumference, and a tendency toward flatter diurnal cortisol rhythms. There were no relations between cortisol slope and psychological or cognitive functioning among patients. In contrast, controls with flatter rhythms showed the expected allostatic load profile of larger waist circumference, poorer performance on explicit memory tasks, lower perceived social support, and a tendency toward higher perceived stress. These findings suggest that the cortisol diurnal slope may have important but different correlates in healthy women versus those with breast cancer.

Winzelberg, A. J., C. Classen, G. W. Alpers, H. Roberts, C. Koopman, R. E. Adams, H. Ernst, P. Dev and C. B. Taylor (2003). "Evaluation of an internet support group for women with primary breast cancer." Cancer 97(5): 1164-73.
BACKGROUND: Women with breast carcinoma commonly experience psychologic distress following their diagnosis. Women who participate in breast cancer support groups have reported significant reduction in their psychologic distress and pain and improvement in the quality of their lives. Web-based breast cancer social support groups are widely used, but little is known of their effectiveness. Preliminary evidence suggests that women benefit from their participation in web-based support groups. METHODS: Seventy-two women with primary breast carcinoma were assigned randomly to a 12-week, web-based, social support group (Bosom Buddies). The group was semistructured, moderated by a health care professional, and delivered in an asynchronous newsgroup format. RESULTS: The results indicate that a web-based support group can be useful in reducing depression and cancer-related trauma, as well as perceived stress, among women with primary breast carcinoma. The effect sizes ranged from 0.38 to 0.54. Participants perceived a variety of benefits and high satisfaction from their participation in the intervention CONCLUSIONS: This study demonstrated that the web-based program, Bosom Buddies, was effective in reducing participants' scores on depression, perceived stress, and cancer-related trauma measures. The effect size of the intervention was in the moderate range. Although web-based social support groups offer many advantages, this delivery mechanism presents a number of ethical issues that need to be addressed.

Butler, L. D., C. Koopman, M. J. Cordova, R. W. Garlan, S. DiMiceli and D. Spiegel (2003). "Psychological distress and pain significantly increase before death in metastatic breast cancer patients." Psychosom Med 65(3): 416-26.
OBJECTIVE: This study was designed to examine the course of psychological distress and pain from study entry to death in 59 women with metastatic breast cancer participating in a randomized trial of the effects of group psychotherapy on psychosocial outcomes and survival. It was hypothesized that psychological distress would increase significantly before death independent of changes in pain. METHOD: Data were collected as part of a larger study (N = 125). Analyses were based on data from a subset of women who had died and for whom we had data from at least three assessments. Mean levels of mood, trauma symptoms, depression symptoms, well-being, and pain over three time points were examined: at baseline (T1), the second-to-last assessment before death (T2), and the last assessment before death (T3). RESULTS: Results indicate that while psychological distress remained relatively constant or declined from T1 to T2, means on all measures significantly changed in the hypothesized direction from T2 to T3. Neither self-reported pain, nor the passage of time, appeared to account for these changes. Additionally, participation in group psychotherapy did not have a significant impact on this change in distress proximal to death. CONCLUSIONS: Results suggest that specialized end-stage clinical interventions are particularly needed for cancer patients as they approach death. Moreover, intervention studies for patients with deteriorating illnesses may need to take this "spike" in psychological distress and pain proximal to death into account to avoid Type II errors in evaluations of psychological outcomes.

Angell, K. L., M. A. Kreshka, R. McCoy, P. Donnelly, J. M. Turner-Cobb, K. Graddy, H. C. Kraemer and C. Koopman (2003). "Psychosocial intervention for rural women with breast cancer: The Sierra-Stanford Partnership." J Gen Intern Med 18(7): 499-507.
OBJECTIVE: This study was initiated by breast cancer survivors living in a rural community in California. They formed a partnership with academic researchers to develop and evaluate a low-cost, community-based Workbook-Journal (WBJ) for improving psychosocial functioning in geographically and economically isolated women with primary breast cancer. DESIGN: A randomized controlled trial was used to compare the WBJ intervention plus educational materials to educational materials alone (usual care). SETTING: One rural cancer center and several private medical, surgical, and radiation oncology practices in 7 rural counties in the Sierra Nevada Foothills of California. PARTICIPANTS: One hundred women with primary breast cancer who were either within 3 months of diagnosis or within 3 months of completing treatment. INTERVENTION: A community-initiated, theoretically-based Workbook-Journal, designed by rural breast cancer survivors and providers as a support group alternative. It included compelling personal stories, local rural resources, coping strategies, and messages of hope. RESULTS: Community recruiters enrolled 83% of the women referred to the study. Retention at 3-month follow-up was 98%. There were no main effects for the WBJ. However, 3 significant interactions suggested that women who were treated in rural practices reported decreased fighting spirit and increased emotional venting and posttraumatic stress disorder symptoms if they did not receive the WBJ. Among women who receive the WBJ, 74% felt emotionally supported. CONCLUSIONS: This community-based Workbook-Journal may be an effective psychosocial intervention for rural, isolated, and low-income women with breast cancer. Community involvement was essential to the success of this project.

Koopman, C., B. Nouriani, V. Erickson, R. Anupindi, L. D. Butler, M. H. Bachmann, S. E. Sephton and D. Spiegel (2002). "Sleep disturbances in women with metastatic breast cancer." Breast J 8(6): 362-70.
We examined sleeping problems in women with metastatic breast cancer in relation to depression, social support, and salivary cortisol. Ninety-seven women with metastatic breast cancer were drawn from a larger study on the effects of group therapy on quality of life and survival. This study is based on the baseline assessments conducted prior to randomization into treatment conditions. Sleep, depression symptoms, and social support were assessed by self-reporting. Cortisol was assessed from saliva samples taken over a 3-day period. Medical status and demographic characteristics were also examined in relation to each sleep variable in multiple regression analysis. Most women (63%) reported one or more types of sleep disturbance and 37% reported using sleeping pills in the previous 30 days. Problems with falling to sleep were significantly related to greater pain and depressive symptoms. Problems of waking during the night were significantly associated with greater depression and less education. Problems in waking/getting up were significantly associated with greater depressive symptoms and less social support. Sleepiness during the day was not significantly related to the variables in the regression model. Fewer hours of sleep were significantly associated with metastases to the bone, higher depressive symptoms, and more social support. Women who reported sleeping 9 or more hours per night, compared to those who reported a moderate amount of sleep (6.5-8.5 hours), had significantly lower 9 p.m. cortisol levels. Use of sleeping pills was more frequent among women reporting greater pain and depressive symptoms. These results suggest that women with metastatic breast cancer who are at higher risk for having sleeping problems are those who are less educated, in pain, depressed, have bony metastases, or lack social support.

Koopman, C., L. D. Butler, C. Classen, J. Giese-Davis, G. R. Morrow, J. Westendorf, T. Banerjee and D. Spiegel (2002). "Traumatic stress symptoms among women with recently diagnosed primary breast cancer." J Trauma Stress 15(4): 277-87.
This study examined the concurrent and longitudinal relationships between traumatic stress symptoms and demographic, medical, and psychosocial variables among women recently diagnosed with primary breast cancer. Participants were 117 women drawn from a parent study for women recently diagnosed with primary breast cancer. At baseline, the Impact of Event Scale (IES) total score was related to intensity of postsurgical treatment and lower emotional self-efficacy. At the 6-month follow-up, the IES total score was significantly related to younger age, to the increased impact of the illness on life, and to the baseline IES total score assessment. These results suggest that it is important to intervene for traumatic stress symptoms soon after the diagnosis of breast cancer. Furthermore, these results suggest women at greatest risk are those who are younger, who receive postsurgical cancer treatment, who are low in emotional self-efficacy and whose lives are most affected by having cancer.

Spiegel, D. and S. E. Sephton (2001). "Psychoneuroimmune and endocrine pathways in cancer: effects of stress and support." Semin Clin Neuropsychiatry 6(4): 252-65.
The bulk of cancer research has productively focused on the pathophysiology of the disease, emphasizing tumor biology, especially tumor characteristics such as DNA ploidy and estrogen/progesterone receptor status as predictors of disease outcome, at the expense of studying the body's psychophysiological reactions to tumor invasion. These reactions are mediated by brain/body mechanisms, including the endocrine, neuroimmune, and autonomic nervous systems. Although a large portion of the variance in any disease outcome is accounted for by the specific local pathophysiology of that disease, some variability must also be explained by 'host resistance' factors, which include the manner of response to the stress of the illness. The evidence of links between social support, stress, emotional state, and immune and endocrine function is growing. Here we examine evidence that 2 especially promising mechanisms, one immune, one endocrine, may mediate the relationship between stress and social support on the one hand and cancer progression on the other. We chose natural killer (NK) cells and cortisol because they are particularly good examples of mediating mechanisms for which there is solid basic and clinical evidence. NK cells are of great interest because they are involved in tumor surveillance, and because their activity can be measured in vitro.

Spiegel, D. (2001). "Mind matters. Coping and cancer progression." J Psychosom Res 50(5): 287-90.
The idea that having an 'attitude' about cancer makes a difference in its course is a popular but controversial one. Most oncologists and surgeons believe that tumor type and stage, general health, and medical treatment are all that account for the variance in outcome. Many patients and their families believe that having the right attitude makes a difference in the course of disease. This leads us to two empirical questions: (1) Does coping make a difference in disease progression when medical prognostic variables are taken into account? and (2) What constitutes the 'right attitude'?

Giese-Davis, J. and D. Spiegel (2001). "Suppression, repressive-defensiveness, restraint, and distress in metastatic breast cancer: separable or inseparable constructs?" J Pers 69(3): 417-49.
A longstanding hypothesis links affective and behavioral inhibition with cancer incidence and progression though it does not clarify psychometric distinctions among related constructs. We hypothesized that repressive-defensiveness, suppression, restraint, and distress would be separable factors in our sample of metastatic breast cancer patients. Our results support the discriminant validity of these constructs in our total sample, and the stability over 1 year in our control group. Using factor analysis, we found 4 separate factors at our prerandomization baseline corresponding closely to hypothesized constructs. Additionally, associations in a multi-trait, multi-occasion (baseline and 1 year) matrix met each of the 3 Campbell and Fiske (1959) criteria of convergent and discriminant validity. Future research testing the links between psychological, physiological, and survival outcomes with affective inhibition in cancer patients will be clearer when informed by these distinctions.

Fobair, P., K. O'Hanlan, C. Koopman, C. Classen, S. Dimiceli, N. Drooker, D. Warner, H. Davids, J. Loulan, D. Wallsten, D. Goffinet, G. Morrow and D. Spiegel (2001). "Comparison of lesbian and heterosexual women's response to newly diagnosed breast cancer." Psychooncology 10(1): 40-51.
In a study comparing lesbian and heterosexual women's response to newly diagnosed breast cancer, we compared data from 29 lesbians with 246 heterosexual women with breast cancer. Our hypotheses were that lesbian breast cancer patients would report higher scores of mood disturbance; suffer fewer problems with body image and sexual activity; show more expressiveness and cohesiveness and less conflict with their partners; would find social support from their partners and friends; and would have a poorer perception of the medical care system than heterosexual women. Our predictions regarding sexual orientation differences were supported for results regarding body image, social support, and medical care. There were no differences in mood, sexual activity or relational issues. Not predicted were differences in coping, indicating areas of emotional strength and vulnerability among the lesbian sample.

Classen, C., L. D. Butler, C. Koopman, E. Miller, S. DiMiceli, J. Giese-Davis, P. Fobair, R. W. Carlson, H. C. Kraemer and D. Spiegel (2001). "Supportive-expressive group therapy and distress in patients with metastatic breast cancer: a randomized clinical intervention trial." Arch Gen Psychiatry 58(5): 494-501.
BACKGROUND: Metastatic breast cancer carries with it considerable psychosocial morbidity. Studies have shown that some patients with metastatic breast cancer experience clinically significant anxiety and depression and traumatic stress symptoms. Supportive-expressive group psychotherapy was developed to help patients with cancer face and adjust to their existential concerns, express and manage disease-related emotions, increase social support, enhance relationships with family and physicians, and improve symptom control. METHODS: Of 125 women with metastatic breast cancer recruited into the study, 64 were randomized to the intervention and 61 to the control condition. Intervention women were offered 1 year of weekly supportive-expressive group therapy and educational materials. Control women received educational materials only. Participants were assessed at baseline and every 4 months during the first year. Data at baseline and from at least 1 assessment were collected from 102 participants during this 12-month period, and these participants compose the study population. RESULTS: Primary analyses based on all available data indicated that participants in the treatment condition showed a significantly greater decline in traumatic stress symptoms on the Impact of Event Scale (effect size, 0.25) compared with the control condition, but there was no difference in Profile of Mood States total mood disturbance. However, when the final assessment occurring within a year of death was removed, a secondary analysis showed a significantly greater decline in total mood disturbance (effect size, 0.25) and traumatic stress symptoms (effect size, 0.33) for the treatment condition compared with the control condition. CONCLUSION: Supportive-expressive therapy, with its emphasis on providing support and helping patients face and deal with their disease-related stress, can help reduce distress in patients with metastatic breast cancer.

Turner-Cobb, J. M., S. E. Sephton, C. Koopman, J. Blake-Mortimer and D. Spiegel (2000). "Social support and salivary cortisol in women with metastatic breast cancer." Psychosom Med 62(3): 337-45.
OBJECTIVE: This study used a cross-sectional design to examine the relationships between social support, both quantity (number of people) and quality (appraisal, belonging, tangible, and self-esteem), and neuroendocrine function (mean and slope of diurnal salivary cortisol) among women with metastatic breast cancer. METHODS: Participants (N = 103) were drawn from a study (N = 125) of the effects of group therapy on emotional adjustment and health in women with metastatic breast cancer. They completed the Interpersonal Support Evaluation List and the Yale Social Support Index and provided saliva samples for assessment of diurnal cortisol levels on each of 3 consecutive days. Diurnal mean levels were calculated using log-transformed cortisol concentrations, and the slope of diurnal cortisol variation was calculated by regression of log-transformed cortisol concentrations on sample collection time. RESULTS: Mean salivary cortisol was negatively related to the Interpersonal Support Evaluation List subscales of appraisal, belonging, and tangible social support. No association was found between quantitative support or the esteem subscale of the Interpersonal Support Evaluation List and mean salivary cortisol. Measures of qualitative and quantitative social support were not associated with the diurnal cortisol slope. CONCLUSIONS: Results show that greater quality of social support is associated with lower cortisol concentrations in women with metastatic breast cancer, which is indicative of healthier neuroendocrine functioning. These results may have clinical implications in the treatment of breast cancer.

Butler, L. D., C. Koopman, C. Classen and D. Spiegel (1999). "Traumatic stress, life events, and emotional support in women with metastatic breast cancer: cancer-related traumatic stress symptoms associated with past and current stressors." Health Psychol 18(6): 555-60.
This study examined levels of intrusion and avoidance symptoms and their relationships to past life stress, current emotional support, disease-related variables, and age in 125 women with metastatic breast cancer. The results indicate that a sizable proportion of these women experienced clinically significant levels of intrusion and avoidance symptoms related to their cancer, particularly those with both more stressful past life events and higher current levels of aversive emotional support. Additionally, both types of symptoms were associated with shorter time since recurrence, and avoidance symptoms were associated with smaller emotional support networks. These results indicate that metastatic breast cancer is an emotionally traumatic event for a significant proportion of women, particularly those with past life stressors and unsupportive social environments.

Spiegel, D., S. E. Sephton, A. I. Terr and D. P. Stites (1998). "Effects of psychosocial treatment in prolonging cancer survival may be mediated by neuroimmune pathways." Ann N Y Acad Sci 840: 674-83.
Research has provided growing evidence of links between the social environment and cancer progression. Indeed, social support in the form of marriage, frequent daily contact with others, and the presence of a confidant may all have protective value against cancer progression. Furthermore, retrospective data suggest that major stressful life events are more prevalent in patients with relapse or malignancy, and thus may contribute to cancer morbidity. Initial studies of the effects of psychosocial intervention with cancer patients have provided some promising results. In three randomized prospective trials, protective effects of psychosocial interventions on cancer progression have been confirmed, while one matching and one randomized study showed no survival effect after psychosocial treatment. Though more research is clearly needed in this area, this body of evidence suggests that psychosocial factors have potentially powerful modulating effects on the course of disease. Here we review evidence of one possible mechanism whereby psychosocial factors may influence disease-resistance capabilities: the neuroimmune connection. Suppressive effects of stress on immune function are well documented, and these effects have been shown to be modulated by social support. Thus, it is reasonable to hypothesize that supportive social relationships may buffer the effects of cancer-related stress on immunity, and thereby facilitate the recovery of immune mechanisms that may be important for cancer resistance. Data addressing this hypothesis are reviewed.

Koopman, C., K. Hermanson, S. Diamond, K. Angell and D. Spiegel (1998). "Social support, life stress, pain and emotional adjustment to advanced breast cancer." Psychooncology 7(2): 101-11.
The purpose of this study was to examine relationships between emotional adjustment to advanced breast cancer, pain, social support, and life stress. The cross-sectional sample was compromised of 102 women with metastatic and/or recurrent breast cancer who were recruited into a randomized psychosocial intervention study. All women completed baseline questionnaires assessing demographic and medical variables, social support, life stress, pain, and mood disturbance. Three types of social support were assessed: (1) number of persons in support system; (2) positive support; and (3) aversive support. On the Profile of Mood States (POMS) total score, we found significant interactions between life stress and social support; having more people in the patient's support system was associated with less mood disturbance, but only among patients who had undergone greater life stress. Also, aversive social contact was significantly related to total mood disturbance (POMS), and having more aversive social contact was particularly associated with total mood disturbance (POMS) among patients who had undergone greater life stress. Pain intensity was associated with greater total life stress, and was not significantly related to social support. These results are consistent with the 'buffering hypothesis' that social support may shield women with metastatic breast cancer from the effects of previous life stress on their emotional adjustment; however, aversive support may be an additional source of life stress associated with emotional distress. Also, pain is greater among women with greater life stress, regardless of social support.

Spiegel, D. (1997). "Psychosocial aspects of breast cancer treatment." Semin Oncol 24(1 Suppl 1): S1-36-S1-47.
Social stress, psychological distress, and psychosocial support effect the adjustment of breast cancer patients, influence their experience of and adherence to medical treatment, and may effect the course of the disease. The literature indicates that levels of distress, depression, and anxiety are substantially elevated among patients with breast cancer. These problems persist in a sizable minority of patients even years after diagnosis. Coping styles are related to adjustment and, in some studies, survival time. The nature of the relationship with physicians affects adjustment to the illness, satisfaction with treatment outcome, and adherence to medical treatment protocols, which can influence relapse and survival. In many but not all studies, serious life stress adversely affects medical outcome. Social support in general and structured psychotherapy in particular have been shown to positively affect both adjustment and survival time. Clear and open communication, expression of appropriate emotion, and collaborative planning and problem-solving enhance adjustment and improve outcome. Conversely, influences that isolate breast cancer patients from others or undermine support can have adverse medical and psychological consequences.

Spiegel, D. and P. M. Kato (1996). "Psychosocial influences on cancer incidence and progression." Harv Rev Psychiatry 4(1): 10-26.
The impact of psychosocial factors on the incidence and progression of cancer has become an area that demands attention. In this article recent evidence of psychosocial effects on cancer incidence and progression is reviewed in the context of past research. Psychosocial factors discussed include personality, depression, emotional expression, social support, and stress. Mechanisms that could mediate the relationship between psychosocial conditions and cancer incidence and progression are also reviewed. These include alterations in diet, exercise, and circadian cycles; variations in medical treatment received; and physiological mechanisms such as psychoendocrinologic and psychoneuroimmunologic effects. We conclude that there is a nonrandom relationship among various psychosocial factors and cancer incidence and progression that can only partially be explained by behavioral, structural, or biological factors. Suggestions for future research are discussed.

Spiegel, D. (1996). "Psychological distress and disease course for women with breast cancer: one answer, many questions." J Natl Cancer Inst 88(10): 629-31.

Spiegel, D. (1996). "Cancer and depression." Br J Psychiatry Suppl(30): 109-16.
Half of all cancer patients have a psychiatric disorder, usually an adjustment disorder with depression. Anxiety about illness, such as cancer, often leads to delay in diagnosis, which has been estimated to reduce prospects of long-term cancer survival by 10% to 20%. Although earlier studies showed that depressed individuals were at higher risk for cancer incidence, later studies have not confirmed this predictive relationship. Nonetheless, effective psychotherapeutic treatment for depression has been found to affect the course of cancer. Psychotherapy for medically ill patients results in reduced anxiety and depression, and often pain reduction. In three randomised studies, psychotherapy resulted in longer survival time for patients with breast cancer (18 months), lymphoma, and malignant melanoma. The physiological mechanisms for these findings have not yet been determined, but four fundamental possibilities for psychotherapeutic effects on physiological change include health maintenance behaviour, health-care utilisation, endocrine environment, and immune function. Thus, effective treatment of depression in cancer patients results in better patient adjustment, reduced symptoms, reduced cost of care, and may influence disease course. The treatment of depression in these patients may be considered a part of medical as well as psychiatric treatment.

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