Exploring the relationship between DNA methylation age measures and psychoneurological symptoms in women with early-stage breast cancer.

PURPOSE: The epigenetic clock has been acknowledged as an indicator for molecular aging, but few studies have examined possible associations of DNA methylation (DNAm) age or age acceleration (AA) with symptom burden in individuals who are treated for cancer. This study explored the association of DNAm age or AA with psychoneurological (PN) symptoms, including cognitive impairment, fatigue, sleep disturbances, pain, and depressive symptoms, in breast cancer survivors over a 2-year period. METHODS: We measured PN symptoms using reliable instruments and DNAm levels by Infinium HumanMethylation450K BeadChip (N = 72). DNAm age was calculated by the Horvath, Grim, and Hannum-based intrinsic and extrinsic age estimations. AA was defined by the residual regressing estimated epigenetic age on chronological age. Mixed regression models were fitted for AA and changes in AA to study the association over time. Separate linear regression models and a mixed-effects model were fitted for AA at each time point. RESULTS: Horvath-AA, Grim-AA, and extrinsic epigenetic AA were significantly changed over time, while intrinsic epigenetic AA did not exhibit any temporal changes. Increased AA was associated with greater anxiety and fatigue, as well as worse cognitive memory, adjusting for race, BMI, income, chemotherapy, radiation therapy, and chronological age. Increased DNAm age was associated with greater anxiety over 2 years. CONCLUSION: Our findings suggest DNAm age and AA may be associated with PN symptoms over the course of cancer treatment and survivorship. Some PN symptoms may be amenable to preventive interventions targeted to epigenetic clocks that influence aging-associated processes.

Longitudinal Analysis of Sleep Disturbance in Breast Cancer Survivors.

BACKGROUND: Breast cancer survivors (BCS) often report poor sleep quality and wakefulness throughout the night as the greatest challenges experienced during and posttreatment. OBJECTIVES: This study aimed to elucidate characteristics of sleep disturbances and determine potential predictors that affect sleep disturbances in BCS for 2 years postchemotherapy. METHODS: This is a secondary analysis of data from the EPIGEN study, which longitudinally examined sociodemographic and cancer-related factors, lifestyle, symptom characteristics, and epigenetic factors at baseline prior to chemotherapy (T1), the midpoint (T2), 6-month (T3), 1-year (T4), and 2-year (T5) time points postchemotherapy. Temporal lifestyle changes, symptom characteristics, and epigenetic factors were explored using linear mixed-effects models with a random intercept. A linear regression model was fitted to identify significant predictors of sleep disturbances at each time point. RESULTS: In 74 BCS with an average age of 51 years and 70% non-Hispanic White, BCS experienced severe sleep disturbances at T2, which gradually improved over time. Significant temporal changes in midsleep awakenings, early awakenings, and fatigue at work were observed, with disturbances being elevated at T2. Anxiety (T1, T2, and T4), fatigue (T3 and T4), and perceived stress (T3) were significant predictors after adjusting for radiation therapy, surgery, and adjuvant endocrine therapy. DISCUSSION: This study highlights that predictors of sleep disturbances change over time, with anxiety being a factor earlier in the treatment trajectory (prechemotherapy) and continuing over time with fatigue and perceived stress being involved later in the treatment trajectory. Our results indicate that symptom management strategies to address sleep disturbances should be tailored to the temporal factors that may change in severity during active treatment and early survivorship period. Findings gained from this study on sleep disturbance patterns and the potential risk factors can be incorporated into clinical practice in planning education and developing interventions.

Global Metabolomics in Allogeneic Hematopoietic Cell Transplantation Recipients Discordant for Chronic Graft-versus-Host Disease.

Chronic graft-versus-host disease (cGVHD) remains a significant late effect issue for allogeneic hematopoietic cell transplantation (allo-HCT) survivors, contributing to morbidity and mortality. The etiology of cGVHD is not well elucidated. Owing to a lack of early diagnostic tests and pathophysiology ambiguity, targeted treatments remain limited. Biomarkers for prediction, control response, or prognostication have not yet been identified. Metabolomics, the quantification of metabolites, is a potential biomarker of cGVHD but has not been evaluated in this population. In this study, we examined global metabolites of stored plasma to identify differentially expressed metabolites of individuals discordant for cGVHD following allo-HCT. A descriptive, comparative, cross-sectional study design was used to examine differentially expressed metabolites of plasma samples obtained from 40 adult allo-HCT recipients (20 with cGVHD and 20 without cGVHD) from 2 parent studies. Metabolomics profiling was conducted at the University of Florida's Southeast Center for Integrative Metabolomics. Full experimental methods followed a previously published method. All statistical analyses were performed by a PhD-prepared, trained bioinformatics statistician. There were 10 differentially expressed metabolites between participants with cGVHD and those without cGVHD. Differential metabolites included those related to energy metabolism (n = 3), amino acid metabolism (n = 3), lipid metabolism (n = 2), caffeine metabolism (n = 1), and neurotransmission (n = 1). Serotonin had the greatest fold change (21.01). This study suggests that cGVHD may be associated with expanded cellular energy and potentially mitochondrial dysfunction. The differential metabolic profile between patients with and without cGVHD indicates metabolic perturbations that merit further exploration as potential biomarkers of cGVHD. These findings support the need for further examination using a larger, prospective study design to identify metabolomic risk factors that may signal the need for earlier preventive measures and earlier treatment to reduce cGVHD.

A scoping review of psychological distress instruments in women with early-stage breast cancer during chemotherapy.

BACKGROUND: Psychological distress is associated with worsening symptoms during the active treatment period and lower quality of life in women with early-stage breast cancer. Many studies have indicated risk for heightened psychological distress across the breast cancer trajectory. PURPOSE: The aim of this review is to examine the literature for instruments used to measure psychological distress among women with breast cancer during chemotherapy. METHODS: This study used the Arksey and O'Malley framework of scoping reviews. Two databases, PubMed & CINAHL, were searched for peer-reviewed original articles that were published within the last ten years, included participants with a diagnosis of breast cancer stages I to III, and receiving chemotherapy, English text articles, and studies that report psychological distress measures. FINDINGS: The initial screening yielded 529 relevant studies. After applying the exclusion criteria, a total of 17 studies concerning the assessment of psychological distress during chemotherapy were retained for the analysis of variables and measures of psychological distress. The instruments used to measure psychological distress varied, with a total of 21 measures. The most frequently utilized measure was the Hospital Anxiety and Depression Scale (n = 5), followed by the Impact of Event Scale (n = 2), the Distress Thermometer (n = 2), and the Perceived Stress Scale (n = 2). CONCLUSION: This review identified the gaps related to inconsistencies in the operationalization and instruments used to measure psychological distress among breast cancer survivors during chemotherapy. Standardization of measures assessing psychological distress, along with conceptual clarity, is essential for measuring distress in research and clinical practice.

Pandemic-Related Innovations in Oncology Nursing Research: Seeking the Positive.

In March 2020, scientists across industry, academic, and healthcare settings were forced to halt their ongoing research studies because of isolation mandates associated with the management of contagion in the COVID-19 pandemi.

Self-Efficacy for Symptom Management in Long-Term Adult Hematopoietic Stem Cell Survivors.

Hematopoietic cell transplantation (HCT) survivors have a complex and multiphase recovery period. Health care delivery and psychosocial interventions for HCT survivors are challenging because many HCT recipients live great distances from the facility where they had their HCT. Therefore identifying factors associated with a patient's capability to self-manage symptoms is a significant focus of survivorship research. A patient's self-efficacy may be important for the successful management of major stressors associated with treatments and recovery. Here, we aimed to evaluate the impact of perceived self-efficacy on distress, quality of life (QoL), depression, and fatigue and identify the factors associated with lower self-efficacy. This cross-sectional study analyzed baseline data from a randomized controlled trial INSPIRE (NCT01602211) in adult (age 18 and older) survivors 2 to 10 years after HCT. Patients with recurrence or subsequent malignancy requiring cancer treatment during the 2 years before enrollment, inability to read and understand English, and lack of access to email and the Internet were excluded. Data included medical records and patient-reported outcomes including Cancer and Treatment Distress (CTXD) with 6 subscales, Patient Health Questionnaire depression scale (PHQ-8), Short Form 12 Health Survey (SF-12) physical function and mental function scores, Brief Fatigue Inventory (BFI) and Self-Efficacy. Pearson correlations were used to test bivariate associations for self-efficacy of CTXD, SF-12, BFI, and PHQ-8. General linear models were used to test the independent associations for CTXD and SF-12 outcomes with self-efficacy, controlling for selected sociodemographic and treatment covariates. Tenability of statistical model assumptions were examined, and no remediation was necessary. A total of 1078 HCT survivors were included in the analysis. Participants were 19 to 85 years (mean age 58), 53% male, and over 90% White and non-Hispanic. Only 16% reported living in a rural area. A majority received an autologous HCT (55%) and were less than 5 years from their first HCT (54%). Among the allogeneic HCT recipients, more than half (55%) had active chronic Graft-versus-Host (cGVHD) and nearly 40% were on active systemic treatment. The mean self-efficacy score was 3.01 (SD = 0.49). Female sex (P = .014), younger age at HCT, younger age at cGVHD presentation (P = .031), moderate to severe currently active cGVHD (P = .003) and household income less than $40,000 (P< .001) were associated with lower self-efficacy. In bivariate analyses, self-efficacy was negatively correlated with mean total distress (CTXD, r = -.5, P< .001) and each of the CTXD subscales. HCT survivors with higher self-efficacy also reported better physical (r 0.48, P< .001) and mental function on the SF-12 (r = 0.57, P< .001). Moreover, self-efficacy was negatively correlated with symptoms such as fatigue (r = -.44, P< .001) and depression (r = -.48, P< .001). In a regression model investigating the impact of self-efficacy on CTXD controlled for demographics and disease characteristics, lower self-efficacy was independently associated with higher distress (CTXD, ß = -.232; 95% CI [-.294, -.169], P< .001). Moreover, there was a significant positive relationship between self-efficacy and both mental (ß = 4.68; 95% CI [3.82, 5.54]; P< .001) and physical (ß = 2.69; 95% CI [1.74, 3.64]; P< .001) components of QoL. Our study demonstrates that lower levels of self-efficacy reported by HCT survivors were independently associated with higher levels of symptoms such as fatigue and depression, lower QoL, and more cancer-related distress. Furthermore, self-efficacy was more likely to be impaired in females, younger adults, those with lower incomes, and survivors with active cGVHD. These findings support the value of self-management interventions focused on improving self-efficacy as having the potential to improve multiple symptoms and QoL in HCT survivors.

Differential DNA methylation following chemotherapy for breast cancer is associated with lack of memory improvement at one year.

The biological basis underlying cognitive dysfunction in women with early-stage breast cancer (BC) remains unclear, but could reflect gene expression changes that arise from the acquisition and long-term retention of soma-wide alterations in DNA methylation in response to chemotherapy. In this longitudinal study, we identified differences in peripheral methylation patterns present in women prior to treatment (T1) and 1 year after receiving chemotherapy (T4) and evaluated relationships among the differential methylation (DM) ratios with changes in cognitive function. A total of 58 paired (T1 and T4) blood specimens were evaluated. Methylation values were determined for DNA isolated from whole blood using a genome-wide array . Cognitive function was measured using the validated, computerized CNS Vital Signs platform. Relationships between methylation patterns and cognitive domain scores were compared using a stepwise linear regression analysis, with demographic variables as covariates. The symptom comparison analysis was restricted to 2,199 CpG positions showing significant methylation ratio changes between T1 and T4. The positions with DM were enriched for genes involved in the modulation of cytokine concentrations. Significant DM ratios were associated with memory domain (56 CpGs). Eight of the ten largest DM ratio changes associated with lack of memory improvement were localized to genes involved in either neural function (ECE2, PPFIBP2) or signalling processes (USP6NL, RIPOR2, KLF5, UBE2V1, DGKA, RPS6KA1). These results suggest that epigenetic changes acquired and retained for at least one year in non-tumour cells following chemotherapy may be associated with a lack of memory improvement following treatment in BC survivors.

Lifestyle Behaviors, Perceived Stress, and Inflammation of Individuals With Chronic Graft-Versus-Host Disease.

BACKGROUND: Stress is a potent immunomodulator contributing to chronic conditions. Chronic graft-versus-host disease (cGVHD) is a life-threatening late effect of allogeneic hematopoietic cell transplantation associated with stress and exaggerated immune response that may be associated to lifestyle behaviors. OBJECTIVE: The aim of this study is to explore associations among lifestyle behaviors, perceived stress, and inflammation of individuals with cGVHD. METHODS: A secondary analysis from a prospective observational study of 24 adults (≥18 years) with cGVHD was conducted. Demographic, clinical, and symptom data were assessed using medical records and validated self-report measures; inflammatory markers were assessed using multiplex and enzyme-linked-immunosorbent assays from plasma. RESULTS: Spiritual growth and total perceived stress were correlated (P < .001). Nutrition and C-reactive protein were negatively correlated (P = .02). Physical activity and cytokines (interleukin [IL]-2, IL-4, IL-5, IL-7, IL-10, IL-12, IL-13, IL-17, and granulocyte colony-stimulating factor) were associated (P < .05). Perceived stress and inflammatory markers were not associated. Individuals did not routinely engage in assessed health-promoting lifestyle behaviors. CONCLUSION: Associations in this sample were noted among lifestyle behaviors, perceived stress, and inflammation. Given these promising findings, further research with a larger sample size is needed to test these associations. Activity, nutrition, stress management, and social support interventions may reduce stress and inflammation. Particularly, connecting with one's higher-self may reduce levels of perceived stress. Finding ways to engage survivors in healthy lifestyle behaviors should be explored. IMPLICATIONS FOR PRACTICE: Information from this study allows nurses to be informed about the role of lifestyle behaviors on inflammation and stress to provide anticipatory guidance to HCT survivors regarding lifestyle choices that may mitigate inflammation and stress to promote positive health outcomes.

Biological Basis for the Clustering of Symptoms.

OBJECTIVES: Identification of biologic pathways of symptom clusters is necessary to develop precision therapies for distressing symptoms. This review examined extant literature evaluating relationships between biomarkers and symptom clusters in cancer survivors. DATA SOURCES: PubMed, CINAHL, Web of Science and Cochrane Library were searched using terms "biological markers" or "biomarkers" and "symptom cluster" or "symptom complex" or "multiple symptoms." CONCLUSION: Biomarkers related to inflammation (eg, cytokines) were the most studied and showed the most significant relationships with clusters of symptoms. This review suggests that clustering of symptoms related to cancer or cancer therapy is linked to immune/inflammatory pathways. IMPLICATIONS FOR NURSING PRACTICE: Understanding the etiology of symptom clusters may guide future nursing interventions for symptom management.

Symptoms, Cytokines, and Quality of Life in Patients Diagnosed with Chronic Graft-Versus-Host Disease Following Allogeneic Hematopoietic Stem Cell Transplantation.

PURPOSE/OBJECTIVES: To describe associations among symptoms, cytokines, and quality of life (QOL) of patients with chronic graft-versus-host disease (cGVHD). DESIGN: Prospective, cross-sectional, cohort. SETTING: The bone marrow transplantation unit at a National Cancer Institute-designated cancer center in Virginia.
 SAMPLE: 24 adults diagnosed with cGVHD. METHODS: Data were collected for demographic factors, symptoms, and QOL from medical record and validated questionnaires. Serum was analyzed for cytokine levels. MAIN RESEARCH VARIABLES: cGVHD, symptoms, cytokines, C-reactive protein, and QOL.
 FINDINGS: Participants reported multiple, concurrent symptoms. Cytokine levels were higher in participants with symptoms versus those without symptoms. Cytokine interleukin-6 correlated with lack of energy and dry mouth. Negative correlations were noted between QOL and symptoms. CONCLUSIONS: Findings demonstrated multiple concurrent symptoms present in this sample and significant relationships among symptoms, cytokines, and QOL. IMPLICATIONS FOR NURSING: cGVHD is a serious condition affecting QOL in many individuals after bone marrow transplantation for many different cancers. Results from this pilot study indicate that patients experience multiple symptoms, including sexual dysfunction, that adversely affect QOL. Better understanding of the interrelated symptoms of cGVHD and the biomarkers associated with these symptoms may lead to targeted symptom management interventions.

Perceptions of Distress in Women with Ovarian Cancer.

PURPOSE/OBJECTIVES: To explore women's experience of distress by asking "What do women with ovarian cancer want their spouse or significant other, family, friends, and healthcare providers to know about their experience of distress during diagnosis and treatment?" RESEARCH APPROACH: Modified Glaserian grounded theory. SETTING: An urban setting in the Mid-Atlantic region of the United States. PARTICIPANTS: 12 women, aged 21-71 years, diagnosed with and treated for ovarian cancer. METHODOLOGIC APPROACH: Constant comparative analysis of data obtained by audio recorded interviews. FINDINGS: Although individual experiences differed, abstraction and conceptualization of the data supported a theory of existential assault. Participants found that the diagnosis was shocking and came "out of the blue like lightning." Their responses included seeking the best physician and treatment available, described as "no stone left unturned." Information about the disease was welcomed and unwelcomed as they shared the experience of "knowing what I don't want to know and not knowing what I want to know," and then had the added experience of sharing that information with those in their social network. Interpersonal interactions were described as "watching you watching me--we are both afraid," and "talking yet not talking about death," resulting in relationship changes and the realization that "now I have to take care of me." CONCLUSIONS: Participants experienced diagnosis with and treatment for ovarian cancer as an existential assault that, with the potential for an early death, affected the individual and her relationships. INTERPRETATION: Previous studies have suggested that women diagnosed with and treated for ovarian cancer experience distress. This study reports women's perceptions of their own distress.