Avanzando Caminos (Leading Pathways): Design and Procedures of The Hispanic/Latino Cancer Survivorship Study.

PURPOSE: Avanzando Caminos (Leading Pathways): The Hispanic/Latino Cancer Survivorship Cohort Study aims to examine the influence of sociocultural, medical, stress, psychosocial, lifestyle, behavioral, and biological factors on symptom burden, health-related quality of life, and clinical outcomes among Hispanics/Latinos who have been previously treated for cancer. METHODS: Avanzando Caminos is a prospective, cohort-based study of 3,000 Hispanics/Latinos who completed primary cancer treatment within the past five years that is representative of the general Hispanic/Latino population in the U.S. Participants will complete self-report measures at baseline (T1), 6 months (T2), 1 year (T3), 2 years (T4), 3 years (T5), 4 years (T6), and 5 years (T7). Blood draws to assess leukocyte gene expression, cardiometabolic markers, and genetic admixture will be collected at baseline (T1), 1 year (T3), 3 years (T5), and 5 years (T7). Medical and cancer characteristics and clinical outcomes will be extracted from the electronic medical record and/or state cancer registry at each time point. Data analysis will include general latent variable modeling and latent growth modeling. CONCLUSIONS: Avanzando Caminos will fill critical gaps in knowledge to guide future secondary and tertiary prevention efforts to mitigate cancer disparities and optimize health-related quality of life among Hispanic/Latino cancer survivors.

Impact of Neighborhood Disadvantage on Tumor Biology and Breast Cancer Survival.

OBJECTIVE: The aim of this study was to evaluate the association between neighborhood disadvantage and Oncotype DX score, a surrogate for tumor biology, among a national cohort. BACKGROUND: Women living in disadvantaged neighborhoods have shorter breast cancer (BC) survival, even after accounting for individual-level, tumor, and treatment characteristics. This suggests unaccounted social and biological mechanisms by which neighborhood disadvantage may impact BC survival. METHODS: This cross-sectional study included stage I and II, ER + /HER2 - BC patients with Oncotype DX score data from the National Cancer Database (NCDB) from 2004 to 2019. Multivariate regression models tested the association of neighborhood-level income on Oncotype DX score controlling for age, race/ethnicity, insurance, clinical stage, and education. Cox regression assessed overall survival. RESULTS: Of the 294,283 total BC patients selected, the majority were non-Hispanic White (n=237,197, 80.6%) with 7.6% non-Hispanic Black (n=22,495) and 4.5% other (n=13,383). 27.1% (n=797,254) of the population lived in the disadvantaged neighborhoods with an annual neighborhood-level income of <$48,000, while 59.62% (n=175,305) lived in advantaged neighborhoods with a neighborhood-level income of >$48,000. On multivariable analysis controlling for age, race/ethnicity, insurance status, neighborhood-level education, and pathologic stage, patients in disadvantaged neighborhoods had greater odds of high-risk versus low-risk Oncotype DX scores compared with those in advantaged neighborhoods [odds ratio=1.04 (1.01-1.07), P =0.0067]. CONCLUSION AND RELEVANCE: This study takes a translational epidemiologic approach to identify that women living in the most disadvantaged neighborhoods have more aggressive tumor biology, as determined by the Oncotype DX score.

ZIP Code to Genomic Code: Neighborhood Disadvantage, Aggressive Breast Cancer Biology, and Breast Cancer Outcomes.

OBJECTIVE: To determine the association between objective (geospatial) and subjective (perceived) measures of neighborhood disadvantage (ND) and aggressive breast cancer tumor biology, defined using validated social adversity-associated transcription factor (TF) activity and clinical outcomes. BACKGROUND: ND is associated with shorter breast cancer recurrence-free survival (RFS), independent of individual, tumor, and treatment characteristics, suggesting potential unaccounted biological mechanisms by which ND influences RFS. METHODS: We quantified TF-binding motif prevalence within promoters of differentially expressed genes for 147 tissue samples prospectively collected on the protocol. Covariate-adjusted multivariable regression analyzed objective and subjective ND scores with 5 validated TFs of social adversity and aggressive biology-pro-inflammatory activity [nuclear factor-κB ( NF-kB ), activator protein 1 ( AP-1 )], sympathetic nervous system (SNS) activity [cyclic 3'-5' adenosine monophosphate response element-binding protein ( CREB )], and protective cellular responses [interferon-regulatory factor ( IRF ) and signal transducer and activator of transcription ( STAT )]. To clinically validate these TFs as prognostic biomarkers of aggressive biology, logistic regression and multivariable Cox proportional-hazards models analyzed their association with Oncotype DX scores and RFS, respectively. RESULTS: Increasing objective ND was associated with aggressive tumor biology (up-regulated NF-kB , activator protein 1, down-regulated IRF , and signal transducer and activator of transcription) and SNS activation (up-regulated CREB ). Increasing subjective ND (eg, threat to safety) was associated with up-regulated NF-kB and CREB and down-regulated IRF . These TF patterns were associated with high-risk Oncotype DX scores and shorter RFS. CONCLUSIONS: In the largest human social genomics study, objective and subjective ND were significantly associated with TFs of aggressive biology and SNS activation. These TFs also correlated with worse clinical outcomes, implicating SNS activation as one potential mechanism behind ND survival disparities. These findings remain to be validated in a national cohort.

Identification of patient subgroups who benefit from a behavioral intervention to improve adjuvant endocrine therapy adherence: a randomized-controlled trial.

PURPOSE: Adjuvant endocrine therapy (AET) reduces breast cancer morbidity and mortality; however, adherence is suboptimal. Interventions exist, yet few have improved adherence. Patient characteristics may alter uptake of an intervention to boost adherence. We examined moderators of the effect of a virtual intervention (STRIDE; #NCT03837496) on AET adherence after breast cancer. METHODS: At a large academic medical center, patients taking AET (N = 100; Mage = 56.1, 91% White) were randomized to receive STRIDE versus medication monitoring. All stored their medication in digital pill bottles (MEMS Caps) which captured objective adherence. Participants self-reported adherence (Medication Adherence Report Scale) at 12 weeks post-baseline. Moderators included age, anxiety, and depressive symptoms (Hospital Anxiety and Depression Scale), AET-related symptom distress (Breast Cancer Prevention Trial Symptom Scale), and AET-specific concerns (Beliefs about Medications Questionnaire). We used hierarchical linear modeling (time × condition × moderator) and multiple regression (condition × moderator) to test the interaction effects on adherence. RESULTS: Age (B = 0.05, SE = 0.02, p = 0.003) and AET-related symptom distress (B = -0.04, SE = 0.02, p = 0.02) moderated condition effect on self-reported adherence while anxiety (B = -1.20, SE = 0.53, p = 0.03) and depressive symptoms (B = -1.65, SE = 0.65, p = 0.01) moderated objective adherence effects. AET-specific concerns approached significance (B = 0.91, SE = 0.57, p = 0.12). Participants who received STRIDE and were older or presented with lower anxiety and depressive symptoms or AET-related symptom distress exhibited improved adherence. Post hoc analyses revealed high correlations among most moderators. CONCLUSIONS: A subgroup of patients who received STRIDE exhibited improvements in AET adherence. The interrelatedness of moderators suggests an underlying profile of patients with lower symptom burden who benefitted most from the intervention. STUDY REGISTRATION: NCT03837496.

Stress Management Interventions to Facilitate Psychological and Physiological Adaptation and Optimal Health Outcomes in Cancer Patients and Survivors.

Cancer diagnosis and treatment constitute profoundly stressful experiences involving unique and common challenges that generate uncertainty, fear, and emotional distress. Individuals with cancer must cope with multiple stressors, from the point of diagnosis through surgical and adjuvant treatments and into survivorship, that require substantial psychological and physiological adaptation. This can take a toll on quality of life and well-being and may also promote cellular and molecular changes that can exacerbate physical symptoms and facilitate tumor growth and metastasis, thereby contributing to negative long-term health outcomes. Since modifying responses tostressors might improve psychological and physiological adaptation, quality of life, and clinical health outcomes, several randomized controlled trials have tested interventions that aim to facilitate stress management. We review evidence for the effects of stress management interventions on psychological and physiological adaptation and health outcomes in cancer patients and survivors and summarize emerging research in the field to address unanswered questions.

Familism, family cohesion, and health-related quality of life in Hispanic prostate cancer survivors.

BACKGROUND: Familism, the cultural value that emphasizes feelings of loyalty and dedication to one's family, has been related to both positive and negative outcomes in Hispanic cancer survivors. One potential source of observed inconsistencies may be limited attention to the family environment, as familism may be protective in a cohesive family whereas it can exacerbate distress in a conflictive family. PURPOSE: The current study explored the associations of familism with general and disease-specific health-related quality of life (HRQoL) in Hispanic men who completed prostate cancer (PC) treatment, and whether family cohesion may help explain these relationships. METHODS: Hispanic men treated for localized PC (e.g., radiation, surgery) were enrolled in a randomized controlled stress management trial and assessed prior to randomization. Familism (familial obligation) was assessed using Sabogal's Familism Scale and family cohesion was measured using the Family Environment Scale (ranging from high to low). The sexual, urinary incontinence, and urinary obstructive/irritative domains of the Expanded Prostate Cancer Index Composite - Short Form measured disease-specific HRQoL. The physical, emotional, and functional well-being subscales of the Functional Assessment of Cancer Therapy - General captured general HRQoL. Hierarchical linear regression and the SPSS PROCESS macro were used to conduct moderation analyses, while controlling for relevant covariates. RESULTS: Participants were 202 older men on average 65.7 years of age (SD = 8.0) who had been diagnosed with PC an average of 22 months prior to enrollment. Familism was not directly associated with general and disease-specific HRQoL. Moderation analyses revealed that greater familism was related to poorer urinary functioning in the incontinence (p = .03) and irritative/obstructive domains (p = .01), and lower emotional well-being (p = .02), particularly when family cohesion was low. CONCLUSIONS: These findings underscore the importance of considering contextual factors, such as family cohesion, in understanding the influence of familism on general and disease-specific HRQoL among Hispanic PC patients. The combined influence of familism and family cohesion predicts clinically meaningful differences in urinary functioning and emotional well-being during the posttreatment phase. Culturally sensitive psychosocial interventions to boost family cohesion and leverage the positive impact of familistic attitudes are needed to enhance HRQoL outcomes in this population.

The Impact of HIV Infection on Neoadjuvant and Adjuvant Chemotherapy Relative Dose Intensity in South African Patients with Breast Cancer.

INTRODUCTION: In the South African Breast Cancer and HIV Outcomes (SABCHO) study, we previously found that breast cancer patients living with HIV and treated with neoadjuvant chemotherapy achieve lower rates of complete pathologic response than patients without HIV. We now assess the impact of comorbid HIV on receipt of timely and complete neoadjuvant and adjuvant chemotherapy. MATERIALS AND METHODS: Since June 2015, the SABCHO study has collected data on women diagnosed with breast cancer at 6 South African hospitals. We selected a sample of participants with stages I-III cancer who received ≥2 doses of neoadjuvant or adjuvant chemotherapy. Data on chemotherapies prescribed and received, filgrastim receipt, and laboratory values measured during treatment were captured from patients' medical records. We calculated the mean relative dose intensity (RDI) for all prescribed chemotherapies. We tested for association between full regimen RDI and HIV status, using linear regression to control for demographic and clinical covariates, and for association of HIV with laboratory abnormalities. RESULTS: The 166 participants living with HIV and 159 without HIV did not differ in median chemotherapy RDI: 0.89 (interquartile range (IQR) 0.77-0.95) among those living with HIV and 0.87 (IQR 0.77-0.94) among women without HIV. Patients living with HIV experienced more grade 3+ anemia and leukopenia than those without HIV (anemia: 10.8% vs. 1.9%, P = .001; leukopenia: 8.4% vs. 1.9%, P = .008) and were more likely to receive filgrastim (24.7% vs. 10.7%, P = .001). CONCLUSIONS: HIV status did not impact neoadjuvant or adjuvant chemotherapy RDI, although patients with breast cancer living with HIV experienced more myelotoxicity during treatment.

Effects of neighborhood disadvantage on cortisol and interviewer-rated anxiety symptoms in breast cancer patients initiating treatment.

PURPOSE: Shorter breast cancer (BC) survival outcomes persist by neighborhood disadvantage independent of patient, tumor, and treatment characteristics. This suggests unaccounted mechanisms by which neighborhood disadvantage "gets under the skin" to impact BC survival outcomes. Here, we evaluate the relationship between neighborhood disadvantage and clinical and neuroendocrine markers of stress in BC patients. METHODS: Women with stage 0-III BC were enrolled 2-10 weeks post-surgery and before initiating adjuvant treatment in a study examining stress and stress management processes. Women provided an afternoon-evening (PM) serum cortisol sample and were administered the Hamilton Anxiety Rating Scale (HAM-A). Home addresses were used to determine the Area Deprivation Index (ADI), a validated measure of neighborhood disadvantage. Multiple regression assessed the relationship between ADI and PM serum cortisol and the presence of elevated HAM-A symptoms. RESULTS: Our sample (n = 225) was predominately middle-aged (M = 50.4 years; range 23-70 years), non-Hispanic White (64.3%), with stage I (38.1%), or II (38.6%) disease. The majority (n = 175) lived in advantaged neighborhoods (ADI 1-3). After controlling for age, stage, and surgery type, women from high ADI (4-10) (vs low ADI) neighborhoods had higher PM cortisol levels (ß = 0.19, 95% CI [0.24, 5.00], p = 0.031) and were nearly two times as likely to report the presence of elevated anxiety symptoms (OR = 1.96, 95% CI [1.00, 3.86], p = 0.050). CONCLUSION: Neighborhood disadvantage is significantly associated with higher levels of PM cortisol and elevated anxiety symptoms suggesting stress pathways could potentially contribute to relationships between neighborhood disadvantage and BC survival.

Correlates of posttraumatic stress in cancer patients and their family caregivers across two years following diagnosis.

OBJECTIVE: To examine risk-factors of cancer-related PTSS in the 2-years post-diagnosis in adult colorectal cancer patients and caregivers. METHODS: Patients with colorectal cancer and their caregivers (N = 130 dyads) self-reported sociodemographic, psychosocial, and medical factors at diagnosis/treatment initiation (T1), at 1- (T2), and 2-year (T3) post-diagnosis. Cancer-related PTSS were assessed, and path analysis examined associations between proposed correlates and PTSS. RESULTS: Among patients, higher neuroticism and greater physical symptom distress were concurrently associated with higher PTSS (Bs ≥ 0.10, ps ≤ 0.02); greater physical symptom distress at T1 and greater social support at T2 were associated with higher PTSS at T3 (Bs ≥ 0.37, ps ≤ 0.04). Among caregivers, female gender, higher neuroticism (Bs ≥ 0.12, ps < 0.01), and lower social support (Bs  ≤ -0.24, ps ≤ 0.02) were associated with higher concurrent PTSS; lower patient physical symptom distress and social support at T1 (Bs  ≤ -0.27, ps ≤ 0.03) and longer hours spent caregiving at T2 (B = 0.03, p = 0.05) were associated with higher PTSS at T3. CONCLUSIONS: Findings identify cancer-specific risk factors (physical symptoms, hours caregiving), in addition to established risk factors (female, neuroticism, social support) in non-medical populations. The identified subgroups should receive ongoing screening and psychosocial referral for cancer-related PTSS.

Predictors of initial engagement with an asynchronous cognitive behavioral stress management website among older women with nonmetastatic breast cancer.

PURPOSE: Digital interventions, like websites, offer greater access to psychosocial treatments; however, engagement is often suboptimal. Initial use may be a target to "hook" participants. Few studies examine engagement with cognitive behavioral stress management (CBSM). We tested predictors of engagement in the first week of using a CBSM website among women with breast cancer (BC). METHODS: Older women (≥ 50 years) with nonmetastatic BC enrolled in an on-going trial (8/2016-4/2022, #NCT03955991) and were randomized to receive 10 synchronous, virtual CBSM group sessions immediately (n = 41) or after a 6-month waitlist (n = 34). All received simultaneous access to an asynchronous website, where supplemental videos and resources were released weekly. Engagement was tracked via breadth (features used) and depth (clicks within content). Multilevel modeling tested predictors of engagement (i.e., time, condition, age, daily stress, depression, race, ethnicity, disease stage). RESULTS: Breadth decreased over the first week of CBSM (b = -0.93, p < .01), and women with more advanced stage disease engaged with more breadth (b = 0.52, p < .01) and depth (b = 14.06, p < .01) than women with earlier stage disease. Non-Hispanic (b = -0.59, p = .03) and White (b = -0.97, p < .01) women engaged with more features. Cancer stage and intervention timing interacted. Women with more advanced cancer stage who received CBSM later engaged with the most depth (b = -11.73, p = .04). All other characteristics did not predict engagement. CONCLUSIONS: Disease stage, race, ethnicity, and intervention timing predicted engagement with a CBSM website in older BC patients. IMPLICATIONS FOR CANCER SURVIVORS: Delivering CBSM later in cancer treatment may mitigate competing demands. Fostering greater engagement in racial/ethnic minorities is needed.

Development and initial psychometric evaluation of a COVID-related psychosocial experiences questionnaire for cancer survivors.

BACKGROUND: Cancer survivors are at elevated risk of psychological problems related to COVID-19, yet no published measure adequately assesses their psychosocial experiences during the pandemic. PURPOSE: Describe the development and factor structure of a comprehensive, self-report measure (COVID-19 Practical and Psychosocial Experiences questionnaire [COVID-PPE]) assessing the pandemic's impact on US cancer survivors. METHODS: The sample (n = 10,584) was divided into three groups to assess COVID-PPE factor structure by conducting: (1) initial calibration/exploratory analysis of the factor structure of 37 items (n = 5070), (2) confirmatory factor analysis of the best-fitting model (36 items after item removal; n = 5140), and (3) post-hoc confirmatory analysis with an additional six items not collected in the first two groups (42 items; n = 374). RESULTS: The final COVID-PPE was divided into two sets of subscales, conceptualized as Risk Factors and Protective Factors. The five Risk Factors subscales were labeled Anxiety Symptoms, Depression Symptoms, Health Care Disruptions, Disruptions to Daily Activities and Social Interactions, and Financial Hardship. The four Protective Factors subscales were labeled Perceived Benefits, Provider Satisfaction, Perceived Stress Management Skills, and Social Support. Internal consistency was acceptable for seven subscales (αs = 0.726-0.895; ωs = 0.802-0.895) but poor or questionable for the remaining two subscales (αs = 0.599-0.681; ωs = 0.586-0.692). CONCLUSIONS: To our knowledge, this is the first published self-report measure comprehensively capturing psychosocial impact-both positive and negative-of the pandemic on cancer survivors. Future work should evaluate predictive utility of COVID-PPE subscales, particularly as the pandemic evolves, which may inform recommendations for cancer survivors and facilitate identification of survivors most in need of intervention.

Functions of Resiliency Traits and Processes in Differential Effects of CBSM on Quality of Life in Breast Cancer Survivors: A Moderated Mediation Model.

BACKGROUND: Although there is evidence that cognitive behavioral therapy (CBT)-based group interventions can improve quality of life (QoL) in women undergoing treatment for breast cancer (BC) little is known about factors that mediate and moderate these effects. We examined a) the mediating role of benefit finding on QoL changes after a Cognitive Behavioral Stress Management (CBSM) intervention, and b) whether this mediation effect differed based on baseline optimism in the first year following surgery for BC. METHODS: We used data from a prior CBSM trial in 240 women with stage 0-3 BC who completed measures of benefit finding (Benefit Finding Scale, BFS), QoL (Functional Assessment of Cancer Treatment, FACT-G), and optimism (Life Orientation Test-Revised) at baseline (2 - 10 weeks post-surgery), 6-months and 12-months after randomization. CBSM-related changes and mediation and moderation effects were assessed using latent growth curve models. RESULTS: We found CBSM increased benefit finding (b = 2.65, p < 0.01), emotional (b = 0.53, p < 0.01), and functional QoL (b = 0.71, p < 0.05) over time. CBSM-related changes in emotional QoL were mediated by increased benefit finding (indirect effect = 0.68, 95% bootstrapped CI: 0.17, 1.56) but only among participants with low to moderate optimism at baseline. CONCLUSION: CBSM intervention improved emotional QoL over the first year of breast cancer treatment by increasing benefit finding among women who reported low trait optimism suggesting those who will most likely benefit from improving benefit finding during this stressful period.

A telehealth intervention for symptom management, distress, and adherence to adjuvant endocrine therapy: A randomized controlled trial.

BACKGROUND: Patients taking adjuvant endocrine therapy (AET) after breast cancer face adherence challenges and symptom-related distress. We conducted a randomized trial to evaluate the feasibility, acceptability, and preliminary efficacy of a telehealth intervention (Symptom-Targeted Randomized Intervention for Distress and Adherence to Adjuvant Endocrine Therapy [STRIDE]) for patients taking AET. METHODS: From October 2019 to June 2021, 100 patients reporting difficulty with AET were randomly assigned to either STRIDE or a medication monitoring (MedMon) control group. STRIDE included six weekly small-group videoconferencing sessions and two individual calls. We defined feasibility as having >50% of eligible patients enroll, >70% complete the 12-week assessment, and > 70% of STRIDE patients complete ≥4/6 sessions. We monitored adherence with the Medication Event Monitoring System Caps (MEMS Caps). At baseline and 12- and 24-weeks after baseline, patients self-reported adherence (Medication Adherence Report Scale), AET satisfaction (Cancer Therapy Satisfaction Questionnaire), symptom distress (Breast Cancer Prevention Trial-Symptom Checklist), self-management of symptoms (Self-efficacy for Symptom Management-AET), coping (Measure of Current Status), quality of life (QOL; Functional Assessment of Cancer Therapy-Breast), and mood (Hospital Anxiety and Depression Scale). We used linear mixed effects models to assess the effect of STRIDE on longitudinal outcomes. RESULTS: We enrolled 70.9% (100/141) of eligible patients; 92% completed the 12-week assessment, and 86% completed ≥4/6 STRIDE sessions. Compared with MedMon, STRIDE patients reported less symptom distress (B[difference] = -1.91; 95% CI, -3.29 to -0.52; p = .007) and better self-management of AET symptoms, coping, QOL, and mood. We did not observe significant differences in AET satisfaction or adherence. CONCLUSIONS: STRIDE is feasible and acceptable, showing promise for improving outcomes in patients taking AET after breast cancer. LAY SUMMARY: Patients taking adjuvant endocrine therapy (AET) after breast cancer may face challenges while following their treatment regimen. In this randomized controlled trial of 100 patients taking AET, a brief, small-group virtual intervention (STRIDE) was well-received by patients and led to improvements in how upset patients were due to symptoms, how confident they were in managing symptoms, and how well they could cope with stress. Thus, STRIDE is a promising intervention and should be tested in future multi-site trials.

Structural Racism and Breast Cancer-specific Survival: Impact of Economic and Racial Residential Segregation.

OBJECTIVE: To analyze the effect of economic and racial/ethnic residential segregation on breast cancer-specific survival (BCSS) in South Florida, a diverse metropolitan area that mirrors the projected demographics of many United States regions. SUMMARY BACKGROUND DATA: Despite advances in diagnosis and treatment, racial and economic disparities in BCSS. This study evaluates these disparities through the lens of racial and economic residential segregation, which approximate the impact of structural racism. METHODS: Retrospective cohort study of stage I to IV breast cancer patients treated at our institution from 2005 to 2017. Our exposures include index of concentration at the extremes, a measurement of economic and racial neighborhood segregation, which was computed at the census-tract level using American Community Survey data. The primary outcome was BCSS. RESULTS: Random effects frailty models predicted that patients living in low-income neighborhoods had higher mortality compared to those living in high-income neighborhoods [hazard ratios (HR): 1.56, 95% confidence interval (CI): 1.23-2.00]. Patients living in low-income non-Hispanic Black and Hispanic neighborhoods had higher mortality compared to those living in high-income non-Hispanic White (NHW) neighborhoods (HR: 2.43, 95%CI: 1.72, 3.43) and (HR: 1.99, 95%CI: 1.39, 2.84), after controlling for patient characteristics, respectively. In adjusted race-stratified analysis, NHWs living in low-income non-Hispanic Black neighborhoods had higher mortality compared to NHWs living in high-income NHW neighborhoods (HR: 4.09, 95%CI: 2.34-7.06). CONCLUSIONS: Extreme racial/ethnic and economic segregation were associated with lower BCSS. We add novel insight regarding NHW and Hispanics to a growing body of literature that demonstrate how the ecological effects of structural racism-expressed through poverty and residential segregation-shape cancer survival.

Relationships Between Serum Cortisol, RAGE-Associated s100A8/A9 Levels, and Self-Reported Cancer-Related Distress in Women With Nonmetastatic Breast Cancer.

OBJECTIVE: Elevated inflammation and psychological distress in patients with breast cancer (BCa) have been related to poorer health outcomes. Regulation of the hypothalamic-pituitary-adrenal axis and signaling of the receptor for advanced glycation end products (RAGE) are important in the inflammatory response and have been associated with increased stress and poorer health outcomes in patients with cancer. This study examined relationships among circulating cortisol, a measure of hypothalamic-pituitary-adrenal axis activity and physiological stress; s100A8/A9, a RAGE ligand and emerging cancer-related biological measure; and self-reported cancer-related distress. METHODS: Patients with BCa ( N = 183, stages 0-IIIb) were recruited 2 to 10 weeks after surgery but before receiving adjuvant therapies. Participants provided blood samples, from which serum cortisol and s100A8/A9 levels were determined, and completed a psychosocial questionnaire. Regression analyses, adjusting for age, cancer stage, time since surgery, race, and menopausal status, were conducted examining the relationships between cortisol, s100A8/A9, and cancer-related distress (Impact of Event Scale [IES]-Revised). RESULTS: Cortisol and s100A8/A9 levels were positively related ( ß = 0.218, t (112) = 2.332, p = .021), although the overall model was not significant. Cortisol levels were also positively associated with IES-Intrusions ( ß = 0.192, t (163) = 2.659, p = .009) and IES-Hyperarousal subscale scores ( ß = 0.171, t (163) = 2.304, p = .022). CONCLUSIONS: Patients with higher cortisol levels also reported higher s100A8/A9 levels and more cancer-related distress. The relationship between cortisol and s100A8/A9 supports a link between the stress response and proinflammatory physiological processes known to predict a greater metastatic risk in BCa. Stress processes implicated in cancer biology are complex, and replication and extension of these initial findings are important.

Spiritual well-being, distress and quality of life in Hispanic women diagnosed with cancer undergoing treatment with chemotherapy.

OBJECTIVE: Previous studies have examined whether spiritual well-being is associated with cancer outcomes, but minority populations are under-represented. This study examines associations of baseline spiritual well-being and change in spiritual well-being with change in distress and quality of life, and explores potential factors associated with changes in spiritual well-being among Hispanic women undergoing chemotherapy. METHODS: Participants completed measures examining spiritual well-being, distress, and quality of life prior to beginning chemotherapy and at weeks 7 and 13. Participants' acculturation and sociodemographic data were collected prior to treatment. Mixed models were used to examine the association of baseline spiritual well-being and change in spiritual well-being during treatment with change in distress and quality of life, and to explore whether sociodemographic factors, acculturation and clinical variables were associated with change in spiritual well-being. RESULTS: A total of 242 participants provided data. Greater baseline spiritual well-being was associated with less concurrent distress and better quality of life (p < 0.001), as well as with greater emotional and functional well-being over time (p values < 0.01). Increases in spiritual well-being were associated with improved social well-being during treatment, whereas decreases in spiritual well-being were associated with worsened social well-being (p < 0.01). Married participants reported greater spiritual well-being at baseline relative to non-married participants (p < 0.001). CONCLUSIONS: Greater spiritual well-being is associated with less concurrent distress and better quality of life, as well as with greater emotional, functional, and social well-being over time among Hispanic women undergoing chemotherapy. Future work could include developing culturally targeted spiritual interventions to improve survivors' well-being.

Pain, cancer-related distress, and physical and functional well-being among men with advanced prostate cancer.

PURPOSE: Men with advanced prostate cancer (APC) experience high levels of pain, which contribute to poor psychosocial and functional outcomes. Cancer-related distress explains the relationship between pain severity and interference, yet specificity of distress characteristics (e.g., hyperarousal, intrusive, or avoidant symptoms) in explaining associations between pain experiences and well-being has not been explored within APC. This study examined men with APC entering a clinical trial and tested associations of baseline pain, cancer-related distress, and physical and functional well-being. METHODS: One hundred ninety men with APC enrolled in a randomized-controlled trial and were assessed prior to randomization. The McGill Pain Questionnaire assessed pain severity, and the Functional Assessment of Cancer Therapy-General captures physical and functional well-being. The Impact of Events Scale-Revised measured cancer-specific distress symptoms, including hyperarousal, avoidance, and intrusion symptoms. Controlling for age, cancer stage at diagnosis, income, education, and race/ethnicity, mediation models (SPSS PROCESS, model 4) tested whether cancer-specific distress accounted for the associations between pain severity and physical and functional well-being. RESULTS: Men were on average 68 years of age, White non-Hispanic, with stage IV cancer. Pain severity was related to poorer physical (p < .001) and functional well-being (p < .001). Associations between pain severity and physical and functional well-being were partially mediated by greater intrusive and hyperarousal symptoms but not avoidant symptoms. CONCLUSION: For men with APC, intrusive and hyperarousal symptoms may partially explain the relationship between pain severity and decrements in physical and functional well-being. APC pain management should attend to such distress symptoms, which may contribute to interference if left unaddressed. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03149185.

Development and initial testing of TOGETHER-YA: an eHealth-delivered and group-based psychosocial intervention for young adult cancer survivors.

PURPOSE: This study aimed to (1) develop TOGETHER-YA, an e-Health-delivered and group-based health-related quality of life (HRQOL) intervention for young adult (YA) cancer survivors aged 18-39 (Part 1), and (2) determine its initial feasibility and acceptability in a single-arm pilot trial (Part 2). METHODS: TOGETHER-YA is a manualized, 10-week intervention for YA survivors that includes elements of relaxation training, cognitive-behavioral therapy, and health education. In Part 1, content was adapted from existing evidence-based interventions with feedback from YAs (N = 22) in four iterative focus groups. In Part 2, YA survivors (N = 11) participated in a single-arm pilot trial of TOGETHER-YA. Intervention groups were led by a trained facilitator over videoconference. Primary outcomes were feasibility (i.e., recruitment, session attendance, retention) and acceptability (i.e., participant satisfaction). RESULTS: Focus groups reacted positively to TOGETHER-YA and provided actionable recommendations for enhancing its relevance and acceptability, which were implemented. In initial testing, all feasibility and acceptability benchmarks were met; 58% of eligible YAs were recruited, participants attended M = 6 intervention sessions (SD = 3), and 82% of participants were retained post-intervention. On average, participants "agreed" to "strongly agreed" with positive statements about the weekly sessions and the overall program. CONCLUSION: TOGETHER-YA was developed in collaboration with YA cancer survivors and found to be feasible and acceptable in initial testing. TOGETHER-YA is the first HRQOL intervention for a broad range of YA survivors that is eHealth-delivered for convenience and group-based for peer support. Future large-scale trials should test its efficacy for improving HRQOL. TRIAL REGISTRATION: NCT05048316, September 17, 2021; NCT05054569, September 23, 2021.

Impacts of Cognitive Behavioral Therapy for Insomnia and Pain on Sleep in Women with Gynecologic Malignancies: A Randomized Controlled Trial.

Insomnia is an adverse cancer outcome impacting mood, pain, quality of life, and mortality in cancer patients. Cognitive Behavioral Therapy (CBT) is an evidence-based treatment for diverse psychophysiological disorders, including pain and insomnia. Primarily studied in breast cancer, there is limited research on CBT within gynecology oncology. This study examined CBT effects on subjective and behavioral sleep outcomes: Sleep Efficiency (SE), Sleep Quality (SQ), Total Wake Time (TWT), Sleep Onset Latency (SOL), and Wake After Sleep Onset (WASO). Thirty-five women with insomnia status/post-surgery for gynecologic cancer were randomized to CBT for insomnia and pain (CBTi.p., N = 18) or Psychoeducation (N = 17). Sleep was assessed via sleep diaries and wrist-worn actigraphy at baseline (T1), post-intervention (T2), and two-month follow-up (T3). Intent-to-treat analyses utilizing mixed linear modeling examined longitudinal group differences on sleep controlling for age and advanced cancer. All participants demonstrated improved (1) subjective SE (0.5, p < .01), SOL (-1.2, p < .01), TWT (-1.2, p < .01), and (2) behavioral SE (0.1, p = .02), TWT (-1.2, p = .03), WASO (-0.8, p < .01) across time. Group-level time trends were indicative of higher subjective SE (6.8, p = .02), lower TWT (-40.3, p = .01), and lower SOL (-13.0, p = .05) in CBTi.p. compared to Psychoeducation. Supplemental analyses examining clinical significance and acute treatment effects demonstrated clinical improvements in SE (T1), TWT (T2, T3), and SOL (T3). Remaining effects were not significant. Despite lacking power to detect interaction effects, CBTi.p. clinically improved sleep in women with gynecologic cancers and insomnia during the active treatment phase. Future research will focus on developing larger trials within underserved populations.

Brief relaxation training is associated with long-term endocrine therapy adherence among women with breast cancer: post hoc analysis of a randomized controlled trial.

PURPOSE: Despite life-saving potential, many women struggle to adhere to adjuvant endocrine therapy (AET) for their breast cancer (BCa). Prior research has demonstrated that emotional distress is a barrier to AET adherence. We followed women from a trial to test the long-term effects of two 5-week post-surgical group-based stress management interventions, cognitive behavioral therapy (CBT), and relaxation training versus an attention-matched health education control, on AET adherence. METHODS: We conducted a long-term follow-up (median = 8 years) of women randomized to CBT, relaxation training, or health education after surgery for stage 0-3 BCa. We measured adherence with the Endocrine Therapy Medication Usage Questionnaire (ETMUQ). First, we established factors on the ETMUQ via confirmatory factor analysis. We then used Bayesian structural equation modeling to regress these factors on study arm, controlling for age and treatments received. RESULTS: Of those who completed long-term follow-up (n = 59, 44.7%), over half (n = 33; 55.9%) reported problems with adherence generally. Women receiving relaxation training (n = 15) had better adherence than those receiving health education (n = 24) on the Forgetfulness/Inconsistency [B(SE) = 0.25(0.14), p = 0.049] and Intentional Nonadherence [B(SE) = 0.31(0.14), p = 0.018] factors of the ETMUQ. Similar results were observed for those receiving relaxation training compared to CBT (n = 20): Forgetfulness/Inconsistency [B(SE) = - 0.47(0.25), p = 0.031]; Intentional Nonadherence [B(SE) = - 0.31(0.15), p = 0.027]. CONCLUSION: Women receiving relaxation training were less likely to (1) forget to take their AET and (2) intentionally miss doses of AET in the long term compared to women receiving health education or CBT. This is evidence for the need of randomized trials that aim to improve adherence by incorporating theoretically based behavioral change techniques. TRIAL REGISTRATION AND DATES: Trial 2R01-CA-064710 was registered March 26, 2006.