Association Between Neighborhood Opportunity, Allostatic Load, and All-Cause Mortality in Patients With Breast Cancer.

PURPOSE: Adverse neighborhood contextual factors may affect breast cancer outcomes through environmental, psychosocial, and biological pathways. The objective of this study is to examine the relationship between allostatic load (AL), neighborhood opportunity, and all-cause mortality among patients with breast cancer. METHODS: Women age 18 years and older with newly diagnosed stage I-III breast cancer who received surgical treatment between January 1, 2012, and December 31, 2020, at a National Cancer Institute Comprehensive Cancer Center were identified. Neighborhood opportunity was operationalized using the 2014-2018 Ohio Opportunity Index (OOI), a composite measure derived from neighborhood level transportation, education, employment, health, housing, crime, and environment. Logistic and Cox regression models tested associations between the OOI, AL, and all-cause mortality. RESULTS: The study cohort included 4,089 patients. Residence in neighborhoods with low OOI was associated with high AL (adjusted odds ratio, 1.21 [95% CI, 1.05 to 1.40]). On adjusted analysis, low OOI was associated with greater risk of all-cause mortality (adjusted hazard ratio [aHR], 1.45 [95% CI, 1.11 to 1.89]). Relative to the highest (99th percentile) level of opportunity, risk of all-cause mortality steeply increased up to the 70th percentile, at which point the rate of increase plateaued. There was no interaction between the composite OOI and AL on all-cause mortality (P = .12). However, there was a higher mortality risk among patients with high AL residing in lower-opportunity environments (aHR, 1.96), but not in higher-opportunity environments (aHR, 1.02; P interaction = .02). CONCLUSION: Lower neighborhood opportunity was associated with higher AL and greater risk of all-cause mortality among patients with breast cancer. Additionally, environmental factors and AL interacted to influence all-cause mortality. Future studies should focus on interventions at the neighborhood and individual level to address socioeconomically based disparities in breast cancer.

Association of Allostatic Load With All-Cause Mortality in Patients With Breast Cancer.

Importance: Elevated allostatic load (AL) has been associated with adverse socioenvironmental stressors and tumor characteristics that convey poor prognosis in patients with breast cancer. Currently, the association between AL and all-cause mortality in patients with breast cancer is unknown. Objective: To examine the association between AL and all-cause mortality in patients with breast cancer. Design, Setting, and Participants: This cohort study used data from an institutional electronic medical record and cancer registry at the National Cancer Institute Comprehensive Cancer Center. Participants were patients with breast cancer diagnoses (stage I-III) between January 1, 2012, through December 31, 2020. Data were analyzed from April 2022 through November 2022. Exposure: AL was expressed as a summary score calculated by assigning 1 point for biomarkers in the worst sample quartile. High AL was defined as AL greater than the median. Main Outcomes and Measures: The main outcome was all-cause mortality. A Cox proportional hazard models with robust variance tested the association between AL and all-cause mortality. Results: There were 4459 patients (median [IQR] age, 59 [49-67] years) with an ethnoracial distribution of 3 Hispanic Black patients (0.1%), 381 non-Hispanic Black patients (8.5%), 23 Hispanic White patients (0.5%), 3861 non-Hispanic White patients (86.6%), 27 Hispanic patients with other race (0.6%), and 164 non-Hispanic patients with other race (3.7%). The mean (SD) AL was 2.6 (1.7). Black patients (adjusted relative ratio [aRR], those with 1.11; 95% CI, 1.04-1.18), single marital status (aRR, 1.06; 95% CI, 1.00-1.12), and those with government-supplied insured (Medicaid aRR, 1.14; 95% CI, 1.07-1.21; Medicare aRR, 1.11; 95% CI, 1.03-1.19) had a higher adjusted mean AL than those who were White, married/living as married, or privately insured, respectively. Adjusting for sociodemographic, clinical, and treatment factors, high AL was associated with a 46% increase in mortality risk (hazard ratio [HR], 1.46; 95% CI, 1.11-1.93) over low AL. Similarly, compared with patients in the first AL quartile, those in the third quartile (HR, 1.53; 95% CI, 1.07-2.18) and the fourth quartile (HR, 1.79; 95% CI, 1.16-2.75) had significantly increased risks of mortality. There was a significant dose-dependent association between increased AL and a higher risk of all-cause mortality. Furthermore, AL remained significantly associated with higher all-cause mortality after adjusting for the Charlson Comorbidity Index. Conclusions and Relevance: These findings suggest increased AL is reflective of socioeconomic marginalization and associated with all-cause mortality in patients with breast cancer.

Risk Factors for Immune Checkpoint Inhibitor Immunotherapy Toxicity Among Older Adults with Cancer.

OBJECTIVES: Immune checkpoint inhibitor immunotherapy (IO) is revolutionizing cancer care but can lead to significant toxicity. This study seeks to describe potential risk factors for immune-related adverse events (irAEs) specifically among older adults. MATERIALS AND METHODS: This was a retrospective study at a single academic comprehensive cancer center based on chart review data abstracted by physicians. For patients aged ≥70 years, frequency, type, and grade of irAEs and their association with baseline patient demographics, comorbidities, mobility, and functional status were characterized using bivariate analysis. Based on those results, multivariable logistic regressions were constructed to model the association between these characteristics with any grade and grade 3 or higher irAEs. RESULTS: Data were analyzed for 238 patients aged ≥70 years who received IO for mostly (≥90%) advanced cancer between 2011 and 2018. Thirty-nine percent of older adults experienced an irAE and 13% experienced one that was grade 3 or higher. In the multivariable analysis, depression was associated with an increased incidence of any grade irAE, while decreased life-space mobility was associated with an increased incidence of grade ≥3 irAEs. CONCLUSION: Most characteristics of special interest among older adults, include fall risk, weight loss, cognitive limitations, and hearing loss, were not associated with irAEs in our study. However, decreased life-space mobility and depression are potential risk factors for IO toxicity among older adults with advanced cancer. Interventions designed to evaluate and mitigate modifiable risk factors for treatment-related toxicity are needed, and the results of this study may be useful for guiding those efforts.

Association of Allostatic Load With Overall Mortality Among Patients With Metastatic Non-Small Cell Lung Cancer.

Importance: Adverse social determinants of health (SDHs) (eg, poverty) are associated with poor oncologic outcomes among patients with lung cancer. However, no studies have evaluated biological correlates of adverse SDHs, operationalized as allostatic load (AL), with mortality due to lung cancer. Objective: To examine the association among AL, SDHs, and mortality among patients with metastatic non-small cell lung cancer (NSCLC). Design, Setting, and Participants: This cross-sectional study of an observational cohort was performed at a National Cancer Institute-designated comprehensive cancer center with data accrued from June 1, 2017, to August 31, 2019. Patients with metastatic (stage IV) NSCLC enrolled at diagnosis into a prospective observational cohort study were included in the present analysis if they had all the biomarkers to calculate an AL score (N = 143). Follow-up was completed on August 31, 2021, and data were analyzed from July 1 to September 30, 2021. Exposures: Social determinants of health. Main Outcomes and Measures: Overall mortality and AL. Results: A total of 143 patients met the study criteria with a median age of 63 (IQR, 55-71) years (89 men [62.2%] and 54 women [37.8%]). In terms of race and ethnicity, 1 patient (0.7%) was Asian, 7 (4.9%) were Black, 117 (81.8%) were White, 17 (11.9%) were of multiple races, and 1 (0.7%) was of other race or ethnicity. The mean (SD) AL was 2.90 (1.37). Elevated AL covaried with lower educational level (r = -0.26; P = .002), male sex (r = 0.19; P = .02), limited mobility (r = 0.19; P = .04), worsening self-care (r = 0.30; P < .001), problems engaging in usual activities (r = 0.21; P = .01), depressive symptoms (r = 0.23; P = .005), and a high number of stressful life events (r = 0.30; P < .001). Multivariable analysis found only increasing difficulty with mobility (r = 0.37 [95% CI, 0.13-0.60]; P = .002) and male sex (r = 0.63 [95% CI, 0.19-1.08]; P = .005) associated with higher AL. On adjusted analysis, elevated AL (hazard ratio, 1.43 [95% CI, 1.16-1.79]; P = .001) and low educational level (hazard ratio, 2.11 [95% CI, 1.03-4.34]; P = .04) were associated with worse overall mortality. Conclusions and Relevance: The findings of this cross-sectional study suggest that higher AL was associated with adverse SDHs and worse overall mortality among patients with advanced NSCLC. These results provide a framework for replication and further studies of AL as a biological correlate for SDH and future prognostic marker.

The relation of illness perceptions to stress, depression, and fatigue in patients with chronic lymphocytic leukaemia.

OBJECTIVE: Chronic lymphocytic leukaemia (CLL) is the most prevalent adult leukaemia and is incurable. The course and treatment of CLL is unique and characterised by repeated cycles of treatment, stable disease and relapse. Utilising a Self-Regulatory Model framework, we examined the relationship between patients' illness perceptions and cancer-specific stress, depressive symptoms and fatigue. Our aim was to test illness perceptions as predictors of these outcomes when variance due to disease and treatment variables was controlled. DESIGN: Data were collected on 147 patients with relapsed/refractory CLL as they entered a phase II clinical trial of an investigational medication at a university affiliated, National Cancer Institute designated comprehensive cancer center. MAIN OUTCOME MEASURES: Cancer-specific stress, depressive symptoms and fatigue interference. RESULT: . Hierarchical multiple regression was used. Consequences and emotional representation were related to all outcomes (ps < .01). Illness concern was related to cancer-specific stress (p < .01), and identity was related to fatigue interference (p < .01). All relationships were observed while controlling for number of previous CLL therapies received. CONCLUSION: Illness perceptions are related to cancer-specific stress, depressive symptoms and fatigue interference in relapsed/refractory CLL. Interventions targeted at restructuring maladaptive illness perceptions may have clinical benefit in this population.

Women with breast cancer: self-reported distress in early survivorship.

PURPOSE/OBJECTIVES: To identify and compare levels of distress and sources of problems among patients with breast cancer in early survivorship. DESIGN: Descriptive, cross-sectional. SETTING: A National Cancer Institute-designated comprehensive cancer center. SAMPLE: 100 breast cancer survivors were selected to represent four time points in the cancer trajectory. METHODS: Distress was self-reported using the Distress Thermometer and its 38-item problem list. Analysis of variance and chi-square analyses were performed as appropriate. MAIN RESEARCH VARIABLES: Distress scores, problem reports, and time groups. FINDINGS: Participants scored in range of the cutoff of more than 4 (range = 4.1-5.1) from treatment through three months post-treatment. At six months post-treatment, distress levels were significantly lower. Significant differences were found between groups on the total problem list score (p = 0.007) and emotional (p = 0.01) and physical subscale scores (p = 0.003). CONCLUSIONS: Comparison of groups at different points in the cancer trajectory found similar elevated levels from diagnosis through three months. Distress remained elevated in early survivorship but significantly decreased at six months post-treatment. IMPLICATIONS FOR NURSING: Interventions to reduce or prevent distress may improve outcomes in early survivorship.

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.

Supportive care during treatment for breast cancer: resource allocations in low- and middle-income countries. A Breast Health Global Initiative 2013 consensus statement.

Breast cancer patients may have unmet supportive care needs during treatment, including symptom management of treatment-related toxicities, and educational, psychosocial, and spiritual needs. Delivery of supportive care is often a low priority in low- and middle-income settings, and is also dependent on resources available. This consensus statement describes twelve key recommendations for supportive care during treatment in low- and middle-income countries, identified by an expert international panel as part of the 5th Breast Health Global Initiative (BHGI) Global Summit for Supportive Care, which was held in October 2012, in Vienna, Austria. Panel recommendations are presented in a 4-tier resource-stratified table to illustrate how health systems can provide supportive care services during treatment to breast cancer patients, starting at a basic level of resource allocation and incrementally adding program resources as they become available. These recommendations include: health professional and patient and family education; management of treatment related toxicities, management of treatment-related symptoms of fatigue, insomnia and non-specific pain, and management of psychosocial and spiritual issues related to breast cancer treatment. Establishing supportive care during breast cancer treatment will help ensure that breast cancer patients receive comprehensive care that can help 1) improve adherence to treatment recommendations, 2) manage treatment-related toxicities and other treatment related symptoms, and 3) address the psychosocial and spiritual aspects of breast cancer and breast cancer treatments.

Religious Practice and Spirituality in the Psychological Adjustment of Survivors of Breast Cancer.

Religion and spirituality are resources regularly used by patients with cancer coping with diagnosis and treatment, yet there is little research that examines these factors separately. This study investigated the relationships between religious practice and spirituality and quality of life (QoL) and stress in survivors of breast cancer. The sample included 130 women assessed 2 years following diagnosis. Using hierarchical multiple regression analysis, the authors found that spiritual well-being was significantly associated with QoL and traumatic stress, whereas religious practice was not significantly associated with these variables. The results suggest that it may be helpful for clinicians to address spirituality, in particular with survivors of breast cancer.

Distress reduction from a psychological intervention contributes to improved health for cancer patients.

PURPOSE: Psychological interventions are efficacious in reducing emotional distress for cancer patients. However, it is not clear whether psychological improvements are, in turn, related to improved health. A clinical trial tests whether a psychological intervention for cancer patients can do so, and also tests two routes to achieve better health: (a) reducing patients' Emotional Distress, and/or (b) enhancing their functional immunity. METHODS: Post-surgery, 227 breast cancer patients were randomized to intervention or assessment only Study Arms. Conducted in small groups, intervention sessions were offered weekly for 4 months and followed by monthly sessions for 8 months. Measures included psychological (distress), biological (immune), and health outcomes (performance status and evaluations of patient's symptomatology, including toxicity from cancer treatment, lab values) collected at baseline, 4 months, and 12 months. RESULTS: A path model revealed that intervention participation directly improved health (p<.05) at 12 months. These effects remained when statistically controlling for baseline levels of distress, immunity, and health as well as sociodemographic, disease, and cancer treatment variables. Regarding the mechanisms for achieving better health, support was found for an indirect effect of distress reduction. That is, by specifically lowering intervention patients' distress at 4 months, their health was improved at 12 months (p<.05). Although the intervention simultaneously improved patients' T-cell blastogenesis in response to phytohemagglutinin (PHA), the latter increases were unrelated to improved health. CONCLUSION: A convergence of biobehavioral effects and health improvements were observed. Behavioral change, rather than immunity change, was influential in achieving lower levels of symptomatology and higher functional status. Distress reduction is highlighted as an important mechanism by which health can be improved.

Individual trajectories in stress covary with immunity during recovery from cancer diagnosis and treatments.

Research connects stressful events with altered immune regulation, but the role of subjective stress is uncertain. Using a longitudinal design, we provide a statistically powerful test of the relationship between subjective stress (perceived stress, emotional distress) and immunity (T cell blastogenesis, natural killer cell cytotoxicity, [NKCC]) as individuals adjust to a severe stressor, a cancer diagnosis and its treatments. Women with regional breast cancer (N=113) were assessed at diagnosis/surgery and reassessed 4, 8, 12, and 18 months later. Latent growth curve analysis tested two hypotheses: (1) initial levels of subjective stress will correlate inversely with initial levels of immunity, and (2) rate of change in subjective stress will correlate inversely with rate of change in immunity. As predicted by Hypothesis 1, participants with high initial subjective stress showed poor initial blastogenesis. As predicted by Hypothesis 2, participants exhibiting an early, rapid decline in subjective stress also showed rapid improvement in NKCC. Follow-up analyses revealed perceived stress to be strongly related to immune function, while emotional distress was not. This is the first study to investigate trajectories in stress and immunity during recovery from a major stressor. Results imply that NK and T cells are sensitive to different aspects of the stress response. While T cell blastogenesis correlated with initial (peak) subjective stress, NKCC correlated with change (improvement) in subjective stress. These data highlight the importance of subjective stress, particularly stress appraisals, in the immune response to a major stressor.

Measuring meaning in life following cancer.

Meaning in life is a multi-faceted construct that has been conceptualized in diverse ways. It refers broadly to the value and purpose of life, important life goals, and for some, spirituality. We developed a measure of meaning in life derived from this conceptualization and designed to be a synthesis of relevant theoretical and empirical traditions. Two samples, all cancer patients, provided data for scale development and psychometric study. From exploratory and confirmatory factor analyses the Meaning in Life Scale (MiLS) emerged, and includes four aspects: Harmony and Peace, Life Perspective, Purpose and Goals, Confusion and Lessened Meaning, and Benefits of Spirituality. Supporting data for reliability (internal consistency, test-retest) and construct validity (convergent, discriminant, individual differences) are provided. The MiLS offers a theoretically based and psychometrically sound assessment of meaning in life suitable for use with cancer patients.

TNF-alpha levels in cancer patients relate to social variables.

Tumor necrosis factor-alpha (TNF-alpha) is an important cytokine associated with tumor regression and increased survival time for cancer patients. Research evidence relates immune factors (e.g., natural killer (NK) cell counts, NK cell lysis, lymphocyte profile, and lymphocyte proliferation) to the frequency and quality of social relations among cancer patients. We hypothesized that disruptions in social relations would be associated with lower TNF-alpha responses, and conversely, that reports of positive changes in social relations correlate with stronger responses. A prospective design measured changes in social activity and relationship satisfaction with a partner in 44 breast cancer patients at the time of cancer diagnosis, and initial surgery and 12 months later. Results indicated that patients reporting increased social activities or satisfaction exhibited stronger stimulated TNF-alpha responses. This is the first study to link changes in patient social relations with a cancer-relevant immune variable.

The gynecologic oncology consult: symptom presentation and concurrent symptoms of depression and anxiety.

OBJECTIVE: To detail the relationship of gynecologic symptoms and sociodemographic variables to depression and anxiety reports among women who were referred to gynecologic oncologists for evaluation. METHODS: Consecutive patients (N = 151) from an National Cancer Institute-designated comprehensive cancer center were accrued and participated on the day of consultation. Patients completed measures assessing depression (Center for Epidemiological Studies Depression Scale) and anxiety (Beck Anxiety Inventory) symptoms, common gynecologic signs/symptoms, and sociodemographic characteristics. Patients were followed up and subsequent diagnoses yielded 73 (48%) cancer and 78 (52%) benign cases. RESULTS: Descriptive analyses revealed that the cancer group was significantly older (52 versus 45 years) than the benign group, and variables correlated with age also differed significantly, with the cancer sample more likely to be postmenopausal, unemployed, and if employed, working fewer hours per week. Importantly, the groups did not differ on reports of depressive, anxiety, or gynecologic symptoms. Hierarchical multiple regression analyses, collapsing across groups, yielded significant correlates of emotional distress. Women who were older, without a spouse/partner, and who had more gynecologic symptoms had higher levels of both depressive and anxiety symptoms. Among the women who did have a partner, those with relationships of longer duration reported lower levels of depression/anxiety CONCLUSION: Reports of clinically significant depressive (42%) and anxiety symptoms (30%) were high. The number of gynecologic symptoms was reliably correlated with emotional distress. Age and absence of partner may have conferred added vulnerability. For those women with partners, lengthier relationships appeared to offer protection from both depressive and anxiety symptoms. LEVEL OF EVIDENCE: III