Julienne E. Bower

Psychological resources, positive illusions, and health.

Psychological beliefs such as optimism, personal control, and a sense of meaning are known to be protective of mental health. Are they protective of physical health as well? The authors present a program of research that has tested the implications of cognitive adaptation theory and research on positive illusions for the relation of positive beliefs to disease progression among men infected with HIV. The investigations have revealed that even unrealistically optimistic beliefs about the future may be health protective. The ability to find meaning in the experience is also associated with a less rapid course of illness. Taken together, the research suggests that psychological beliefs such as meaning, control, and optimism act as resources, which may not only preserve mental health in the context of traumatic or life-threatening events but be protective of physical health as well.

Fatigue in breast cancer survivors: occurrence, correlates, and impact on quality of life.

PURPOSE To describe the occurrence of fatigue in a large sample of breast cancer survivors relative to general population norms and to identify demographic, medical, and psychosocial characteristics of fatigued survivors. PATIENTS AND METHODS Breast cancer survivors in two large metropolitan areas completed standardized questionnaires as part of a survey study, including the RAND 36-item Health Survey, Center for Epidemiological Studies-Depression Scale, Breast Cancer Prevention Trial Symptom Checklist, Medical Outcomes Study Sleep Scale, and demographic and treatment-related measures. RESULTS On average, the level of fatigue reported by the breast cancer survivors surveyed (N = 1,957) was comparable to that of age-matched women in the general population, although the breast cancer survivors were somewhat more fatigued than a more demographically similar reference group. Approximately one third of the breast cancer survivors assessed reported more severe fatigue, which was associated with significantly higher levels of depression, pain, and sleep disturbance. In addition, fatigued women were more bothered by menopausal symptoms and were somewhat more likely to have received chemotherapy (with or without radiation therapy) than nonfatigued women. In multivariate analyses, depression and pain emerged as the strongest predictors of fatigue. CONCLUSION Although the majority of breast cancer survivors in this large and diverse sample did not experience heightened levels of fatigue relative to women in the general population, there was a subgroup of survivors who did report more severe and persistent fatigue. We identified characteristics of these women that may be helpful in elucidating the mechanisms underlying fatigue in this population, as well as directing intervention efforts.

Fatigue and Proinflammatory Cytokine Activity in Breast Cancer Survivors

Objective Fatigue is a common problem among cancer patients and survivors, yet the mechanisms underlying the occurrence and persistence of this symptom are not known. Activation of the immune system may evoke feelings of fatigue, which are mediated by proinflammatory cytokines. We examined whether fatigued breast cancer survivors would show elevations in proinflammatory cytokines and markers of cytokine activity compared with nonfatigued survivors. Differences in lymphocyte subsets, cortisol, and behavioral symptoms associated with proinflammatory cytokines were also assessed. Methods Forty breast cancer survivors (20 fatigued, 20 nonfatigued) provided blood samples at visits scheduled to control for diurnal variability. Cytokines, soluble markers of cytokine activity, and cortisol were measured by immunoassay and lymphocyte subsets by flow cytometry. Participants also completed questionnaires measuring demographic, medical, and behavioral variables. Results Fatigued breast cancer survivors had significantly higher serum levels of several markers associated with proinflammatory cytokine activity than nonfatigued survivors, including interleukin-1 receptor antagonist (IL-1ra), soluble tumor necrosis factor receptor type II (sTNF-RII), and neopterin. They were also more likely to report behavioral problems that co-occur with fatigue in the context of immune activation. Fatigued survivors had significantly lower serum levels of cortisol than the nonfatigued group as well as differences in two lymphocyte populations. Conclusions Fatigued breast cancer survivors showed elevations in serum markers associated with proinflammatory cytokine activity an average of 5 years after diagnosis. Results suggest mechanisms through which enduring immune activation may occur, including alterations in cortisol and in lymphocyte subsets.

Breast Cancer in Younger Women: Reproductive and Late Health Effects of Treatment

PURPOSE In 1997, we initiated a cohort study to evaluate quality of life (QOL) and reproductive health outcomes in younger female breast cancer survivors. MATERIALS AND METHODS Using listings from two tumor registries, we recruited women with stage 0, I, or II breast cancer who were 50 years or younger at diagnosis and were also disease-free survivors for 2 to 10 years. A mailed survey questionnaire assessed medical and demographic factors, health-related QOL, mood, outlook on life, and reproductive health outcomes. RESULTS We recruited 577 women, who ranged in age from 30 to 61.6 years (mean, 49.5 years) and were surveyed approximately 6 years after diagnosis. Almost three fourths had received some form of adjuvant therapy. Amenorrhea occurred frequently as a result of treatment in women > or = 40 years at diagnosis, and treatment-associated menopause was associated with poorer health perceptions. Across the cohort, physical functioning was quite good, but the youngest women experienced poorer mental health (P =.0002) and less vitality (energy; P =.03). Multiple regression analyses predicting QOL demonstrated better outcomes in African-American women, married or partnered women, and women with better emotional and physical functioning, whereas women who reported greater vulnerability had poorer QOL. CONCLUSION Overall QOL in younger women who survive breast cancer is good, but there is evidence of increased emotional disruption, especially among the youngest women. Factors that may contribute to poorer health perceptions and QOL include experiencing a menopausal transition as part of therapy, and feeling more vulnerable after cancer.

Cognitive processing, discovery of meaning, CD4 decline, and AIDS-related mortality among bereaved HIV-seropositive men.

This study investigated whether finding meaning in response to an HIV-related stressor was associated with changes in immune status and health. Forty HIV-seropositive men who had recently experienced an AIDS-related bereavement completed interviews assessing cognitive processing and finding meaning after the loss and provided blood samples for a 2- to 3-year follow-up. AIDS-related mortality over an extended follow-up was determined from death certificates. As predicted, men who engaged in cognitive processing were more likely to find meaning from the loss. Furthermore, men who found meaning showed less rapid declines in CD4 T cell levels and lower rates of AIDS-related mortality (all ps < .05), independent of health status at baseline, health behaviors, and other potential confounds. These results suggest that positive responses to stressful events, specifically the discovery of meaning, may be linked to positive immunologic and health outcomes.

Neurocognitive Performance in Breast Cancer Survivors Exposed to Adjuvant Chemotherapy and Tamoxifen

ABSTRACT The primary aim of the current study was to examine whether neurocognitive functioning among breast cancer survivors (BCS) exposed to systemic adjuvant chemotherapy differs from that seen among BCS who did not receive chemotherapy. The performance of each of these BCS groups was compared to a demographically matched comparison group without history of breast cancer, a group not included in the majority of previous cognitive functioning studies. We also sought to explore whether usage of the anti-estrogen drug tamoxifen, a common component of breast cancer treatment, was related to neurocognitive functioning. Finally, we wished to examine the relationship between subjective report of cognitive functioning and objective performance on neurocognitive measures among BCS. Fifty-three survivors of breast cancer (all between 2–5 years after diagnosis and initial surgical removal of cancerous tissue) and 19 healthy non-BCS comparison subjects were administered a comprehensive neurocognitive battery, and measures of mood, energy level, and self-reported cognitive functioning. Those BCS who received adjuvant chemotherapy performed significantly worse in the domains of verbal learning, visuospatial functioning, and visual memory than BCS treated with surgery only. Those who received both chemotherapy and tamoxifen showed the greatest compromise. Although patients who received chemotherapy (with and without tamoxifen) performed worse than those treated with surgery only on several domains, neither group was significantly different from demographically matched comparison subjects without a history of breast cancer. Finally, we found no relationship between subjective cognitive complaints and objective performance, although cognitive complaints were associated with measures of psychological distress and fatigue. We highlight ways in which these data converge with other recent studies to suggest that systemic chemotherapy, especially in combination with tamoxifen, can have adverse yet subtle effects on cognitive functioning.

Quality of Life, Fertility Concerns, and Behavioral Health Outcomes in Younger Breast Cancer Survivors: A Systematic Review

BACKGROUND Breast cancer is the most common cancer in women younger than age 50 years. Cancer treatments in younger women may cause premature menopause, infertility, and negative psychosocial effects. In this systematic review, we examined three key domains of functioning that are particularly relevant for younger breast cancer survivors: health-related quality of life (QOL), menopausal symptoms and fertility concerns, and behavioral health outcomes. METHODS We conducted a literature review using PubMed and secondary sources and examined 840 articles published between January 1990 and July 2010. Inclusion criteria for articles were 1) published in English after 1989; 2) exclusively analyzed female breast cancer survivors aged 50 years or younger or premenopausal at diagnosis, with baseline characteristics and/or quantitative or descriptive analyses for this age group; 3) investigated QOL (health-related QOL including physical functioning and mental health, depression, and anxiety), menopause- or fertility-related concerns, and weight gain or physical activity-related behavioral health outcomes. Data were extracted using a standardized table collecting the purpose, design, population, and results of each study. Extracted data were reviewed for accuracy by two investigators and presented as descriptive tables. RESULTS A total of 28 articles met the inclusion criteria (15 cross-sectional studies, eight longitudinal studies, and five randomized trials). Regarding data review, no discordance between investigators was noted. Standardized measures of QOL and depressive symptoms identified worse outcomes as being more frequent or severe in breast cancer survivors aged 50 years or younger when compared with the general age-matched population of women without cancer and to older women (aged >50 years) with breast cancer. Concerns about premature menopause, menopausal symptoms, and infertility were common in younger women (aged ≤ 50 years) and had a role in the level of distress after treatment. Weight gain and physical inactivity were common health outcomes in younger women. CONCLUSIONS Younger women with breast cancer were found to experience distinct psychosocial and menopause-related concerns, weight gain, and physical inactivity. A need for more longitudinal research, including efforts at intervention to manage these symptoms and adverse health outcomes, remains.

Inflammatory Biomarkers for Persistent Fatigue in Breast Cancer Survivors

Purpose: This study seeks to define immunologic and inflammatory variables associated with persistent post-treatment fatigue in breast cancer survivors. Experimental Design: Leukocyte subsets, plasma inflammatory markers, and ex vivo proinflammatory cytokine production were assessed in 50 fatigued and nonfatigued breast cancer survivors recruited ≥2 years after successful primary therapy. Multivariate statistical analyses were used to define a composite immunologic biomarker of fatigue risk. Results: Fatigued breast cancer survivors were distinguished from nonfatigued survivors by increased ex vivo monocyte production of interleukin (IL)-6 and tumor necrosis factor-α following lipopolysaccharide stimulation, elevated plasma IL-1ra and soluble IL-6 receptor (sIL-6R/CD126), decreased monocyte cell-surface IL-6R, and decreased frequencies of activated T lymphocytes and myeloid dendritic cells in peripheral blood (all P < 0.05). An inverse correlation between sIL-6R and cell-surface IL-6R was consistent with inflammation-mediated shedding of IL-6R, and in vitro studies confirmed that proinflammatory cytokines induced such shedding. Multivariate linear discriminant function analysis identified two immunologic markers, the ratio of sIL-6R to monocyte-associated IL-6R and decreased circulating CD69+ T lymphocytes, as highly diagnostic of fatigue (P = 0.0005), with cross-validation estimates indicating 87% classification accuracy (sensitivity = 0.83; specificity = 0.83). Conclusion: These results extend links between fatigue and inflammatory markers to show a functional alteration in proinflammatory cytokine response to lipopolysaccharide and define a prognostic biomarker of behavioral fatigue.

Inflammation and Behavioral Symptoms After Breast Cancer Treatment: Do Fatigue, Depression, and Sleep Disturbance Share a Common Underlying Mechanism?

PURPOSE Fatigue, depression, and sleep disturbance are common adverse effects of cancer treatment and frequently co-occur. However, the possibility that inflammatory processes may underlie this constellation of symptoms has not been examined. PATIENTS AND METHODS Women (N = 103) who had recently finished primary treatment (ie, surgery, radiation, chemotherapy) for early-stage breast cancer completed self-report scales and provided blood samples for determination of plasma levels of inflammatory markers: soluble tumor necrosis factor (TNF) receptor II (sTNF-RII), interleukin-1 receptor antagonist, and C-reactive protein. RESULTS Symptoms were elevated at the end of treatment; greater than 60% of participants reported clinically significant problems with fatigue and sleep, and 25% reported elevated depressive symptoms. Women treated with chemotherapy endorsed higher levels of all symptoms and also had higher plasma levels of sTNF-RII than women who did not receive chemotherapy (all P < .05). Fatigue was positively associated with sTNF-RII, particularly in the chemotherapy-treated group (P < .05). Depressive symptoms and sleep problems were correlated with fatigue but not with inflammatory markers. CONCLUSION This study confirms high rates of behavioral symptoms in breast cancer survivors, particularly those treated with chemotherapy, and indicates a role for TNF-α signaling as a contributor to postchemotherapy fatigue. Results also suggest that fatigue, sleep disturbance, and depression may stem from distinct biologic processes in post-treatment survivors, with inflammatory signaling contributing relatively specifically to fatigue.

Diurnal cortisol rhythm and fatigue in breast cancer survivors.

Approximately 30% of breast cancer survivors report persistent fatigue of unknown origin. We have previously shown that cancer-related fatigue is associated with alterations in immunological parameters and serum cortisol levels in breast cancer survivors. The current study examined the diurnal rhythm of salivary cortisol in fatigued and non-fatigued breast cancer survivors. Salivary cortisol measures were obtained from breast cancer survivors with persistent fatigue (n=13) and a control group of non-fatigued survivors (n=16). Participants collected saliva samples upon awakening and at 1200, 1700, and 2200 h on two consecutive days. Diurnal cortisol slope for each day was determined by linear regression of log-transformed cortisol values on collection time and analyzed using multi-level modeling. Fatigued breast cancer survivors had a significantly flatter cortisol slope than non-fatigued survivors, with a less rapid decline in cortisol levels in the evening hours. At the individual patient level, survivors who reported the highest levels of fatigue also had the flattest cortisol slopes. Group differences remained significant in analyses controlling for demographic and medical factors, daily health behaviors, and other potential confounds (e.g. depressed mood, body mass index). Results suggest a subtle dysregulation in hypothalamic-pituitary-adrenal axis functioning in breast cancer survivors with persistent fatigue.