A remotely delivered, peer-led intervention to improve physical activity and quality of life in younger breast cancer survivors.

Younger breast cancer survivors (YBCS) consistently report poorer quality of life (QOL) than older survivors. Increasing physical activity (PA) may improve QOL, but this has been understudied in YBCS. This single arm pilot study evaluated the feasibility and acceptability of a 3-month, peer-delivered, remote intervention to increase PA and improve QOL in YBCS. Data were collected from October 2019 - July 2020. Participants (n = 34, 43.1 ± 5.5 years old, 46 ± 34.4 months post-diagnosis, BMI = 30.2 ± 7.4 kg/m2) completed six video sessions with a trained peer mentor; self-monitored PA with a Fitbit activity tracker; and interacted with a private Fitbit Community for social support. At baseline, 3-and 6-months, participants completed QOL questionnaires and PA was measured through accelerometer (moderate-to-vigorous PA [MVPA]) and self-report (strength and flexibility). A parallel mixed-methods approach (qualitative interviews and quantitative satisfaction survey at 3-months) explored intervention feasibility and acceptability. One-way repeated-measures ANOVAs examined impacts on PA and QOL at 3-and 6-months. The intervention was feasible as evidenced by efficient recruitment, high retention, and adherence to intervention components. Remote delivery, working with a peer mentor, and using Fitbit tools were highly acceptable. From baseline to 3-months, participants increased time spent in objectively measured MVPA, strength, and flexibility exercises, and reported meaningful improvements to body image, fatigue, anxiety, and emotional support. A fully remote, peer-to-peer intervention is an acceptable and promising strategy to increase PA and improve QOL in YBCS. Refinements to the intervention and its delivery should be further assessed in future studies, toward the goal of disseminating an evidence-based, scalable intervention to the growing number of YBCS.Trial registration Prospectively registered as NCT04064892.

A randomized trial of physical activity for cognitive functioning in breast cancer survivors: Rationale and study design of I Can! Improving Cognition After Cancer.

INTRODUCTION: Difficulties with cognition are extremely common among breast cancer survivors and can significantly impact quality of life, daily functioning, and ability to return to work. One promising intervention is increasing physical activity, as it has been effective in improving cognition in non-cancer populations. Few physical activity intervention trials with cognition outcomes have included cancer survivors. This project builds upon our previous work indicating that increased physical activity can improve objectively measured processing speed and self-reported cognition among breast cancer survivors. METHODS: The I Can! study will examine whether a physical activity intervention improves cognition among 250 post-treatment breast cancer survivors (Stages I-III, <5 years post-treatment) who are reporting cognitive difficulties. This 2-arm randomized controlled trial comparing a 6-month physical activity intervention (Exercise Group) to a health & wellness attention-comparison condition (Health & Wellness Group) will examine intervention effects on cognition (at 3 and 6 months) and maintenance of effects at 12 months. The primary aim is to investigate the impact of exercise on objectively measured processing speed and self-reported cognition. Secondary aims are to investigate maintenance of cognitive changes and examine candidate biological mechanisms and psychological mediators. CONCLUSION: The I Can! study will contribute to the scientific, public health, and survivorship intervention literature by providing new information on the impact of physical activity for cognitive impairment in breast cancer survivors. Findings from this study will inform guidelines for physical activity to improve the lives of millions of breast cancer survivors.

A Remotely Delivered, Peer-Led Physical Activity Intervention for Younger Breast Cancer Survivors (Pink Body Spirit): Protocol for a Feasibility Study and Mixed Methods Process Evaluation.

BACKGROUND: Younger breast cancer survivors consistently report a greater impact of their cancer experience on quality of life compared with older survivors, including higher rates of body image disturbances, sexual dysfunction, and fatigue. One potential strategy to improve quality of life is through physical activity, but this has been understudied in younger breast cancer survivors, who often decrease their activity during and after cancer treatment. OBJECTIVE: The aim of this study is to explore the feasibility and acceptability of a technology-based, remotely delivered, peer-led physical activity intervention for younger breast cancer survivors. We will also assess the preliminary impact of the intervention on changes in physical activity and multiple aspects of quality of life. METHODS: This study is a community-academic partnership between University of California, San Diego and Haus of Volta, a nonprofit organization that promotes positive self-image in younger breast cancer survivors. This ongoing pilot study aims to recruit 30 younger breast cancer survivors across the United States (<55 years old, >6 months post primary cancer treatment, self-report <60 min of moderate-to-vigorous-intensity physical activity [MVPA]) into a 3-month peer-delivered, fully remote exercise program. Participants will complete 6 biweekly video chat sessions with a trained peer mentor, a fellow younger breast cancer survivor. Participants will receive a Fitbit Charge 3; weekly feedback on Fitbit data from their peer mentor; and access to a private, in-app Fitbit Community to provide and receive support from other participants and all peer mentors. At baseline, 3 months, and 6 months, participants will complete quality of life questionnaires, and MVPA will be measured using the ActiGraph accelerometer. Feasibility and acceptability will be explored through a mixed methods approach (ie, quantitative questionnaires and qualitative interviews). Intervention delivery and adaptations by peer mentors will be tracked through peer mentor self-evaluations and reflections, review of video-recorded mentoring sessions, and monthly templated reflections by the research team. RESULTS: Recruitment began in September 2019. As of February 2020, the physical activity intervention is ongoing. Final measures are expected to occur in summer 2020. CONCLUSIONS: This study explores the potential for physical activity to improve sexual function, body image, and fatigue, key quality of life issues in younger breast cancer survivors. Using peer mentors extends our reach into the young survivor community. The detailed process evaluation of intervention delivery and adaptations by mentors could inform a future hybrid-effectiveness implementation trial. Finally, remote delivery with commercially available technology could promote broader dissemination. TRIAL REGISTRATION: ClinicalTrials.gov NCT04064892; https://clinicaltrials.gov/ct2/show/NCT04064892. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/18420.

Continuous, objective measurement of physical activity during chemotherapy for breast cancer: the Activity in Treatment pilot study.

Despite many potential benefits of physical activity during and after breast cancer treatment, activity levels typically decline from pre- to posttreatment. Most previous research has relied on self-reported activity. The purpose of this study were to assess patterns of daily, to objectively measured physical activity throughout chemotherapy for breast cancer, and to identify predictors of physical activity patterns. Participants were given a Fitbit before starting chemotherapy and asked to wear it throughout chemotherapy. Restricted cubic splines assessed nonlinear patterns of Fitbit measured total physical activity (TPA) and moderate-to-vigorous physical activity (MVPA) throughout the duration of chemotherapy (mean = 17 weeks, standard deviation [SD] = 6.3). Mixed-effects regression models assessed the rate of physical activity decline. Regressions of subject-level random slope assessed predictors of the rate of physical activity decline on participant and cancer characteristics and self-reported physical and cognitive functioning. Participants (n = 32) were on average 50 years old; the majority had stage II breast cancer. MVPA declined linearly at a mean rate of 1.4 min/day (p = .002) for every 10% of chemotherapy completed, whereas TPA declined linearly at an average rate of 13.4 min/day (p = .0007) for every 10% of chemotherapy completed, until around halfway through chemotherapy, when activity rates leveled off. HER+ receptor status was associated with a greater rate of MVPA decline, ß = 13.3, p = .04. This novel study of objectively measured daily MVPA throughout chemotherapy showed that most reductions in activity occurred during the first half of a course of chemotherapy. Targeting this early period of chemotherapy may be important for preventing declines in activity levels throughout chemotherapy.

Mediators of a Physical Activity Intervention on Cognition in Breast Cancer Survivors: Evidence From a Randomized Controlled Trial.

BACKGROUND: Emerging research suggests that increasing physical activity can help improve cognition among breast cancer survivors. However, little is known about the mechanism through which physical activity impacts cancer survivors' cognition. OBJECTIVE: The objective of this secondary analysis examined physical and psychological function potentially linking physical activity with changes in cognition among breast cancer survivors in a randomized controlled trial where the exercise arm had greater improvements in cognition than the control arm. METHODS: A total of 87 sedentary breast cancer survivors were randomized to a 12-week physical activity intervention (n=43) or control condition (n=44). Objectively measured processing speed (National Institutes of Health Toolbox Oral Symbol Digit), self-reported cognition (patient-reported outcomes measurement information system [PROMIS] cognitive abilities), PROMIS measures of physical and psychological function (depression, anxiety, fatigue, and physical functioning), and plasma biomarkers (brain-derived neurotrophic factor, homeostatic model assessment 2 of insulin resistance, and C-reactive protein [CRP]) were collected at baseline and 12 weeks. Linear mixed-effects models tested intervention effects on changes in physical and psychological function variables and biomarkers. Bootstrapping was used to assess mediation. Exploratory analyses examined self-reported cognitive abilities and processing speed as mediators of the intervention effect on physical functioning. RESULTS: Participants in the exercise arm had significantly greater improvements in physical functioning (beta=1.23; 95% CI 2.42 to 0.03; P=.049) and reductions in anxiety (beta=-1.50; 95% CI -0.07 to -2.94; P=.04) than those in the control arm. Anxiety significantly mediated the intervention effect on cognitive abilities (bootstrap 95% CI -1.96 to -0.06), whereas physical functioning did not (bootstrap 95% CI -1.12 to 0.10). Neither anxiety (bootstrap 95% CI -1.18 to 0.74) nor physical functioning (bootstrap 95% CI -2.34 to 0.15) mediated the intervention effect on processing speed. Of the biomarkers, only CRP had greater changes in the exercise arm than the control arm (beta=.253; 95% CI -0.04 to 0.57; P=.09), but CRP was not associated with cognition; therefore, none of the biomarker measures mediated the intervention effect on cognition. Neither cognitive abilities (bootstrap 95% CI -0.06 to 0.68) nor processing speed (bootstrap 95% CI -0.15 to 0.63) mediated the intervention effect on physical function. CONCLUSIONS: Physical activity interventions may improve self-reported cognition by decreasing anxiety. If supported by larger studies, reducing anxiety may be an important target for improving self-reported cognition among cancer survivors. TRIAL REGISTRATION: ClinicalTrials.gov NCT02332876; https://clinicaltrials.gov/ct2/show/NCT02332876.

Breast cancer survivors reduce accelerometer-measured sedentary time in an exercise intervention.

PURPOSE: Cancer survivors are highly sedentary and have low physical activity. How physical activity interventions impact sedentary behavior remains unclear. This secondary analysis examined changes in sedentary behavior among breast cancer survivors participating in a physical activity intervention that significantly increased moderate-to-vigorous physical activity (MVPA). METHODS: Insufficiently active breast cancer survivors were randomized to a 12-week physical activity intervention (exercise arm) or control arm. The intervention focused solely on increasing MVPA with no content targeting sedentary behavior. Total sedentary behavior, light physical activity (LPA), and MVPA were measured at baseline and 12 weeks (ActiGraph GT3X+ accelerometer). Separate linear mixed-effects models tested intervention effects on sedentary behavior, intervention effects on LPA, the relationship between change in MVPA and change in sedentary behavior, and potential moderators of intervention effects on sedentary behavior. RESULTS: The exercise arm had significantly greater reductions in sedentary behavior than the control arm (mean - 24.9 min/day (SD = 5.9) vs. - 4.8 min/day (SD = 5.9), b = - 20.1 (SE = 8.4), p = 0.02). Larger increases in MVPA were associated with larger decreases in sedentary behavior (b = - 1.9 (SE = 0.21), p < 0.001). Women farther out from surgery had significantly greater reductions in sedentary behavior than women closer to surgery (b = - 0.91 (SE = 0.5), p = 0.07). There was no significant group difference in change in LPA from baseline to 12 weeks (b = 5.64 (SE = 7.69), p = 0.48). CONCLUSIONS: Breast cancer survivors in a physical activity intervention reduced total sedentary time in addition to increasing MVPA. IMPLICATIONS FOR CANCER SURVIVORS: Both increasing physical activity and reducing sedentary behavior are needed to promote optimal health in cancer survivors. These results show that MVPA and sedentary behavior could be successfully targeted together, particularly among longer-term cancer survivors. CLINICAL TRIAL REGISTRATION: This study is registered at www.ClinicalTrials.gov (NCT02332876).

Perspectives on the Delirium Experience and Its Burden: Common Themes Among Older Patients, Their Family Caregivers, and Nurses.

BACKGROUND AND OBJECTIVES: While there are qualitative studies examining the delirium-related experiences of patients, family caregivers, and nurses separately, little is known about common aspects of delirium burden among all three groups. We describe common delirium burdens from the perspectives of patients, family caregivers, and nurses. RESEARCH DESIGN AND METHODS: We conducted semistructured qualitative interviews about delirium burden with 18 patients who had recently experienced a delirium episode, with 16 family caregivers, and with 15 nurses who routinely cared for patients with delirium. We recruited participants from a large, urban teaching hospital in Boston, Massachusetts. Interviews were recorded and transcribed. We used interpretive description as the approach to data analysis. RESULTS: We identified three common burden themes of the delirium experience: Symptom Burden (Disorientation, Hallucinations/Delusions, Impaired Communication, Memory Problems, Personality Changes, Sleep Disturbances); Emotional Burden (Anger/Frustration, Emotional Distress, Fear, Guilt, Helplessness); and Situational Burden (Loss of Control, Lack of Attention, Lack of Knowledge, Lack of Resources, Safety Concerns, Unpredictability, Unpreparedness). These burdens arise from different sources among patients, family caregivers, and nurses, with markedly differing perspectives on the burden experience. DISCUSSION AND IMPLICATIONS: Our findings advance the understanding of common burdens of the delirium experience for all groups and offer structure for instrument development and distinct interventions to address the burden of delirium as an individual or group experience. Our work reinforces that no one group experiences delirium in isolation. Delirium is a shared experience that will respond best to systemwide approaches to reduce associated burden.

Kinetics of human brown adipose tissue activation and deactivation.

Brown adipose tissue (BAT) has been identified as a potential target in the treatment and prevention of obesity and metabolic disease. The precise kinetics of BAT activation and the duration of stimulus required to recruit metabolically active BAT, and its subsequent deactivation, are not well-understood. In this clinical trial, 19 healthy adults (BMI: 23.7 ± 0.7 kg/m2, Age: 31.2 ± 2.8 year, 12 female) underwent three different cooling procedures to stimulate BAT glucose uptake, and active BAT volume was determined using 18F-Fluorodeoxyglucose (FDG) PET/CT imaging. We found that 20 min of pre-injection cooling produces activation similar to the standard 60 min (39.9 mL vs. 44.2 mL, p = 0.52), indicating that BAT activity approaches its peak function soon after the initiation of cooling. Furthermore, upon removal of cold exposure, active BAT volume declines (13.6 mL vs. 44.2 mL, p = 0.002), but the deactivation process persists even hours following cessation of cooling. Thus, the kinetics of human BAT thermogenesis are characterized by a rapid increase soon after cold stimulation but a more gradual decline after rewarming. These characteristics reinforce the feasibility of developing mild, short-duration cold exposure to activate BAT and treat obesity and metabolic disease.

Breast cancer treatment and its effects on aging.

Breast cancer is the most common cancer of women in the United States. It is also proving to be one of the most treatable. Early detection, surgical intervention, therapeutic radiation, cytotoxic chemotherapies and molecularly targeted agents are transforming the lives of patients with breast cancer, markedly improving their survival. Although current breast cancer treatments are largely successful in producing cancer remission and extending lifespan, there is concern that these treatments may have long lasting detrimental effects on cancer survivors, in part, through their impact on non-tumor cells. Presently, the impact of breast cancer treatment on normal cells, its impact on cellular function and its effect on the overall function of the individual are incompletely understood. In particular, it is unclear whether breast cancer and/or its treatments are associated with an accelerated aging phenotype. In this review, we consider breast cancer survivorship from the perspective of accelerated aging, and discuss the evidence suggesting that women treated for breast cancer may suffer from an increased rate of physical and cognitive decline that likely corresponds with underlying vulnerabilities of genome instability, epigenetic changes, and cellular senescence.

Patterns of Fitbit Use and Activity Levels Throughout a Physical Activity Intervention: Exploratory Analysis from a Randomized Controlled Trial.

BACKGROUND: There has been a rapid increase in the use of technology-based activity trackers to promote behavior change. However, little is known about how individuals use these trackers on a day-to-day basis or how tracker use relates to increasing physical activity. OBJECTIVE: The aims were to use minute level data collected from a Fitbit tracker throughout a physical activity intervention to examine patterns of Fitbit use and activity and their relationships with success in the intervention based on ActiGraph-measured moderate to vigorous physical activity (MVPA). METHODS: Participants included 42 female breast cancer survivors randomized to the physical activity intervention arm of a 12-week randomized controlled trial. The Fitbit One was worn daily throughout the 12-week intervention. ActiGraph GT3X+ accelerometer was worn for 7 days at baseline (prerandomization) and end of intervention (week 12). Self-reported frequency of looking at activity data on the Fitbit tracker and app or website was collected at week 12. RESULTS: Adherence to wearing the Fitbit was high and stable, with a mean of 88.13% of valid days over 12 weeks (SD 14.49%). Greater adherence to wearing the Fitbit was associated with greater increases in ActiGraph-measured MVPA (binteraction=0.35, P<.001). Participants averaged 182.6 minutes/week (SD 143.9) of MVPA on the Fitbit, with significant variation in MVPA over the 12 weeks (F=1.91, P=.04). The majority (68%, 27/40) of participants reported looking at their tracker or looking at the Fitbit app or website once a day or more. Changes in Actigraph-measured MVPA were associated with frequency of looking at one's data on the tracker (b=-1.36, P=.07) but not significantly associated with frequency of looking at one's data on the app or website (P=.36). CONCLUSIONS: This is one of the first studies to explore the relationship between use of a commercially available activity tracker and success in a physical activity intervention. A deeper understanding of how individuals engage with technology-based trackers may enable us to more effectively use these types of trackers to promote behavior change. TRIAL REGISTRATION: ClinicalTrials.gov NCT02332876; https://clinicaltrials.gov/ct2/show/NCT02332876?term=NCT02332876 &rank=1 (Archived by WebCite at http://www.webcitation.org/6wplEeg8i).

Randomized controlled trial of increasing physical activity on objectively measured and self-reported cognitive functioning among breast cancer survivors: The memory & motion study.

BACKGROUND: Increasing physical activity can improve cognition in healthy and cognitively impaired adults; however, the benefits for cancer survivors are unknown. The current study examined a 12-week physical activity intervention, compared with a control condition, on objective and self-reported cognition among breast cancer survivors. METHODS: Sedentary breast cancer survivors were randomized to an exercise arm (n = 43) or a control arm (n = 44). At baseline and at 12 weeks, objective cognition was measured with the National Institutes of Health Cognitive Toolbox, and self-reported cognition using the Patient-Reported Outcomes Measurement Information System scales. Linear mixed-effects regression models tested intervention effects for changes in cognition scores. RESULTS: On average, participants (n = 87) were aged 57 years (standard deviation, 10.4 years) and were 2.5 years (standard deviation, 1.3 years) post surgery. Scores on the Oral Symbol Digit subscale (a measure of processing speed) evidenced differential improvement in the exercise arm versus the control arm (b = 2.01; P < .05). The between-group differences in improvement on self-reported cognition were not statistically significant but were suggestive of potential group differences. Time since surgery moderated the correlation, and participants who were ≤2 years post surgery had a significantly greater improvement in Oral Symbol Digit score (exercise vs control (b = 4.00; P < .01), but no significant improvement was observed in patients who were >2 years postsurgery (b = -1.19; P = .40). A significant dose response was observed with greater increased physical activity associated with objective and self-reported cognition in the exercise arm. CONCLUSIONS: The exercise intervention significantly improved processing speed, but only among those who had been diagnosed with breast cancer within the past 2 years. Slowed processing speed can have substantial implications for independent functioning, supporting the potential importance of early implementation of an exercise intervention among patients with breast cancer. Cancer 2018;124:192-202. © 2017 American Cancer Society.

Clonal analyses and gene profiling identify genetic biomarkers of the thermogenic potential of human brown and white preadipocytes.

Targeting brown adipose tissue (BAT) content or activity has therapeutic potential for treating obesity and the metabolic syndrome by increasing energy expenditure. However, both inter- and intra-individual differences contribute to heterogeneity in human BAT and potentially to differential thermogenic capacity in human populations. Here we generated clones of brown and white preadipocytes from human neck fat and characterized their adipogenic and thermogenic differentiation. We combined an uncoupling protein 1 (UCP1) reporter system and expression profiling to define novel sets of gene signatures in human preadipocytes that could predict the thermogenic potential of the cells once they were maturated. Knocking out the positive UCP1 regulators, PREX1 and EDNRB, in brown preadipocytes using CRISPR-Cas9 markedly abolished the high level of UCP1 in brown adipocytes differentiated from the preadipocytes. Finally, we were able to prospectively isolate adipose progenitors with great thermogenic potential using the cell surface marker CD29. These data provide new insights into the cellular heterogeneity in human fat and offer potential biomarkers for identifying thermogenically competent preadipocytes.

Activation of human brown adipose tissue by a ß3-adrenergic receptor agonist.

Increasing energy expenditure through activation of endogenous brown adipose tissue (BAT) is a potential approach to treat obesity and diabetes. The class of ß3-adrenergic receptor (AR) agonists stimulates rodent BAT, but this activity has never been demonstrated in humans. Here we determined the ability of 200 mg oral mirabegron (Myrbetriq, Astellas Pharma, Inc.), a ß3-AR agonist currently approved to treat overactive bladder, to stimulate BAT as compared to placebo. Mirabegron led to higher BAT metabolic activity as measured via (18)F-fluorodeoxyglucose ((18)F-FDG) using positron emission tomography (PET) combined with computed tomography (CT) in all twelve healthy male subjects (p = 0.001), and it increased resting metabolic rate (RMR) by 203 ± 40 kcal/day (+13%; p = 0.001). BAT metabolic activity was also a significant predictor of the changes in RMR (p = 0.006). Therefore, a ß3-AR agonist can stimulate human BAT thermogenesis and may be a promising treatment for metabolic disease.

Anatomical localization, gene expression profiling and functional characterization of adult human neck brown fat.

The imbalance between energy intake and expenditure is the underlying cause of the current obesity and diabetes pandemics. Central to these pathologies is the fat depot: white adipose tissue (WAT) stores excess calories, and brown adipose tissue (BAT) consumes fuel for thermogenesis using tissue-specific uncoupling protein 1 (UCP1). BAT was once thought to have a functional role in rodents and human infants only, but it has been recently shown that in response to mild cold exposure, adult human BAT consumes more glucose per gram than any other tissue. In addition to this nonshivering thermogenesis, human BAT may also combat weight gain by becoming more active in the setting of increased whole-body energy intake. This phenomenon of BAT-mediated diet-induced thermogenesis has been observed in rodents and suggests that activation of human BAT could be used as a safe treatment for obesity and metabolic dysregulation. In this study, we isolated anatomically defined neck fat from adult human volunteers and compared its gene expression, differentiation capacity and basal oxygen consumption to different mouse adipose depots. Although the properties of human neck fat vary substantially between individuals, some human samples share many similarities with classical, also called constitutive, rodent BAT.