Effects of aerobic exercise on neurocognitive function in postmenopausal women receiving endocrine therapy for breast cancer: The Exercise Program in Cancer and Cognition randomized controlled trial.

Objective: The Exercise Program in Cancer and Cognition (EPICC) Study was a randomized controlled trial (RCT) designed to determine whether six months of moderate-intensity aerobic exercise improves neurocognitive function in women with breast cancer (BC) receiving endocrine therapy (ET). Methods: Postmenopausal women with hormone receptor+, early-stage BC, within two years post-primary therapy were randomized to the exercise intervention (six months, ≥150 minutes of moderate-intensity aerobic exercise/week) or usual care control condition. Outcomes were assessed at pre-randomization and after intervention completion. Groups were compared using linear mixed-effects modeling. Results: Participants (N=153) were X ¯ = 62.09 ± 8.27 years old, with stage I BC (64.1%) and a median of 4.7 months post-diagnosis. We found a group-by-time interaction (p=0.041) and a trend for the main effect of time (p=0.11) for processing speed with improved performance in the exercise group and no change in the controls. Similar main effects of time were observed for learning and memory (p=0.024) and working memory (p=0.01). Better intervention adherence was associated with improved processing speed (p=0.017). Conclusions: Six months of moderate-intensity aerobic exercise improves processing speed in postmenopausal women with BC receiving ET who initiate exercise within two years of completing primary therapy (surgery +/- chemotherapy). This is the first large-scale study to examine the effects of aerobic exercise on neurocognitive function in women with BC. Additional research is needed to address the long-term effects of aerobic exercise on cognitive function.

Physical activity, cardiorespiratory fitness, and cognitive function in postmenopausal women with breast cancer.

Physical activity may improve cognitive function in women with breast cancer. In a cross-sectional study, we explored the relationship between cognitive function and physical activity (actigraph) and cardiorespiratory fitness (sub-maximal graded exercise test) in 73 postmenopausal women with early stage breast cancer prior to the initiation of systemic adjuvant therapy. Cognitive function was assessed with a standardized battery of neurocognitive measures assessing eight domains. Data were analyzed using partial correlations, controlling for age and total hours of actigraph wear-time. Women were, on average, 63.71 (± 5.3) years of age with 15.47 (± 2.48) years of education. For physical activity, greater average number of steps per day were associated with better attention (r = .262, p = .032) and psychomotor speed (r = .301, p = .011); greater average hours of moderate and moderate/vigorous intensity physical activity were associated with better visual memory (r = .241, p = .049; r = .241, p = .049, respectively); and greater average daily energy expenditure was associated with better visual memory (r = .270, p = .027) and psychomotor speed (r = .292, p = .017). For fitness, higher peak maximum VO2 was associated with better concentration (r = .330, p = .006), verbal memory (r = .241, p = .048), and working memory (r = .281, p = .019). These results suggest that higher levels of physical activity and cardiorespiratory fitness are associated with better cognitive function in postmenopausal women with breast cancer. Randomized controlled trials (RCT) to examine whether physical activity improves cognitive function in women with breast cancer are warranted. These RCTs should also determine the mechanisms of the influence of physical activity on cognitive function. CLINICAL TRIALS REGISTRATION NUMBER: NCT02793921; Date: May 20, 2016.

Trajectories of self-reported cognitive function in postmenopausal women during adjuvant systemic therapy for breast cancer.

OBJECTIVE: In a sample of 368 postmenopausal women, we (1) determined within-cohort and between-cohort relationships between adjuvant systemic therapy for breast cancer and self-reported cognitive function during the first 18 months of therapy and (2) evaluated the influence of co-occurring symptoms, neuropsychological function, and other covariates on relationships. METHODS: We evaluated self-reported cognitive function, using the Patient Assessment of Own Functioning Inventory (PAOFI), and potential covariates (e.g., co-occurring symptom scores and neuropsychological function z-scores) in 158 women receiving aromatase inhibitor (AI) therapy alone, 104 women receiving chemotherapy followed by AI therapy, and 106 non-cancer controls. Patients were assessed before systemic therapy and then every 6 months, for a total of four assessments over 18 months. Controls were assessed at matched time points. Mixed-effects modeling was used to determine longitudinal relationships. RESULTS: Controlling for covariates, patients enrolled before chemotherapy reported poorer global cognitive function (p < 0.001), memory (p < 0.001), language and communication (p < 0.001), and sensorimotor function (p = 0.002) after chemotherapy. These patients reported poorer higher-level cognitive and intellectual functions from before chemotherapy to 12 months after initiation of AI therapy (p < 0.001). Higher levels of depressive symptoms (p < 0.001), anxiety (p < 0.001), and fatigue (p = 0.040) at enrollment were predictors of poorer cognitive function over time. PAOFI total score was a predictor of executive function (p = 0.048) and visual working memory (p = 0.005) z-scores, controlling for covariates. CONCLUSIONS: Findings provide further evidence of poorer self-reported cognitive function after chemotherapy and of relationships between co-occurring symptoms and cognitive changes. AI therapy alone does not have an impact on self-reported cognitive function. Copyright © 2015 John Wiley & Sons, Ltd.

Patterns of change in cognitive function with anastrozole therapy.

BACKGROUND: The purpose of this study was to examine and compare the effects of the first 18 months of anastrozole therapy on cognitive function in women with breast cancer. METHODS: This large, longitudinal cohort study was composed of postmenopausal women with early-stage breast cancer who received chemotherapy plus anastrozole (n = 114) or anastrozole alone (n = 173) and a control group (n = 110). Cognitive function was assessed before systemic therapy and 6, 12, and 18 months after therapy initiation and at comparable time points in controls. RESULTS: The chemotherapy-anastrozole and anastrozole-alone groups had poorer executive function than the controls at nearly all time points (P < .0001 to P = .09). A pattern of deterioration in working memory and concentration was observed during the first 6 months of anastrozole therapy for the chemotherapy-anastrozole group (P < .0001 and P < .0009, respectively) and the anastrozole-alone group (P = .0008 and P = .0002, respectively). This was followed by improved working memory and concentration from 6 to 12 months in both groups. The anastrozole-alone group had a second decline in working memory and concentration from 12 to 18 months after the initiation of therapy (P < .0001 and P = .02, respectively). CONCLUSIONS: Women with breast cancer had poorer executive functioning from the period before therapy through the entire first 18 months of therapy. A pattern of decline in working memory and concentration with initial exposure to anastrozole was observed. Women receiving anastrozole alone had a second deterioration in working memory and concentration from 12 to 18 months after therapy initiation. The longer term effects (>18 months) of anastrozole on cognitive function remain to be determined.

Cardiorespiratory fitness is associated with hippocampal resting state connectivity in women newly diagnosed with breast cancer.

Background: Breast cancer and its treatment are associated with aberrant patterns of resting state functional connectivity (rsFC) between the hippocampus and several areas of the brain, which may account for poorer cognitive outcomes in patients. Higher cardiorespiratory fitness (CRF) has been associated with enhanced rsFC and cognitive performance; however, these associations have not been well studied in breast cancer. We examined the relationship between CRF, rsFC of the hippocampus, and cognitive performance among women newly diagnosed with breast cancer. Methods: Thirty-four postmenopausal women newly diagnosed with Stage 0-IIIa breast cancer (Mage = 63.59 ± 5.73) were enrolled in a 6-month randomized controlled trial of aerobic exercise vs. usual care. During baseline assessments, participants completed functional brain imaging, a submaximal CRF test, and cognitive testing. Whole-brain, seed-based analyses were used to examine the relationship between CRF and hippocampal rsFC, with age, years of education, and framewise displacement included as covariates. Cognition was measured with a battery of validated neurocognitive measures, reduced to seven composite factors. Results: Higher CRF was positively associated with greater rsFC of the hippocampus to a cluster within the dorsomedial and dorsolateral frontal cortex (z-max = 4.37, p = 0.003, cluster extent = 1,020 voxels). Connectivity within cluster peaks was not significantly related to cognitive factors (all ps > 0.05). Discussion: CRF was positively associated with hippocampal rsFC to frontal cortex structures, comprising a network of regions commonly suppressed in breast cancer. Future longitudinal research is needed to explore whether baseline rsFC predicts long-term cognitive resilience in breast cancer.

Obesity, Psychological Distress, and Resting State Connectivity of the Hippocampus and Amygdala Among Women With Early-Stage Breast Cancer.

Objective: Overweight and obesity [body mass index (BMI) ≥ 25 kg/m2] are associated with poorer prognosis among women with breast cancer, and weight gain is common during treatment. Symptoms of depression and anxiety are also highly prevalent in women with breast cancer and may be exacerbated by post-diagnosis weight gain. Altered brain function may underlie psychological distress. Thus, this secondary analysis examined the relationship between BMI, psychological health, and resting state functional connectivity (rsFC) among women with breast cancer. Methods: The sample included 34 post-menopausal women newly diagnosed with Stage 0-IIa breast cancer (Mage = 63.59 ± 5.73) who were enrolled in a 6-month randomized controlled trial of aerobic exercise vs. usual care. At baseline prior to randomization, whole-brain analyses were conducted to evaluate the relationship between BMI and seed-to-voxel rsFC of the hippocampus and amygdala. Connectivity values from significant clusters were then extracted and examined as predictors of self-reported depression and anxiety. Results: Mean BMI was in the obese range (M = 31.83 ± 6.62). For both seeds examined, higher BMI was associated with lower rsFC with regions of prefrontal cortex (PFC), including ventrolateral PFC (vlPFC), dorsolateral PFC, and superior frontal gyrus (z range = 2.85-4.26). Hippocampal connectivity with the vlPFC was negatively correlated with self-reported anxiety (ß = 0.47, p < 0.01). Conclusion: Higher BMI was associated with lower hippocampal and amygdala connectivity to regions of PFC implicated in cognitive control and emotion regulation. BMI-related differences in hippocampal and amygdala connectivity following a recent breast cancer diagnosis may relate to future worsening of psychological functioning during treatment and remission. Additional longitudinal research exploring this hypothesis is warranted.

Hazardous materials on golf courses: experience and knowledge of golf course superintendents and grounds maintenance workers from seven states.

BACKGROUND: The golf course industry has a growing Latino work force. Little occupational health research has addressed this work force. This article examines golf course superintendents' and Latino grounds maintenance workers' pesticide knowledge, beliefs, and safety training. In particular, it focuses on knowledge of and adherence to OSHA Right-to-Know regulations. METHODS: In person, in-depth interviews were conducted with 10 golf course superintendents in five states and with 16 Latino grounds maintenance workers in four states. RESULTS: Few superintendents were in compliance with Right-to-Know regulations or did pesticide safety training with all of their workers. Few workers had any pesticide safety knowledge. Most safety training on golf courses was rudimentary and focused on machine safety, and was usually conducted in the off-season or on rainy days, not before workers were assigned tasks. CONCLUSIONS: More Right-to-Know training is necessary for superintendents and grounds maintenance workers. Culturally and linguistically appropriate Spanish language materials need to be developed or made more widely available to train workers. Better enforcement of safety and training regulations is necessary.

Protocol for Exercise Program in Cancer and Cognition (EPICC): A randomized controlled trial of the effects of aerobic exercise on cognitive function in postmenopausal women with breast cancer receiving aromatase inhibitor therapy.

The Exercise Program in Cancer and Cognition (EPICC) Study is a randomized controlled trial designed to test the effects of moderate-intensity aerobic exercise on cognitive function in postmenopausal women with early-stage breast cancer during the first six months of aromatase inhibitor therapy. It is estimated that up to 75% of survivors of breast cancer experience cognitive impairment related to disease and treatment. At present, there are no known interventions to improve or manage cognitive function for women with breast cancer. Here, we describe a single-blinded, randomized controlled trial with allocation of 254 postmenopausal women with early-stage breast cancer to a supervised six-month aerobic exercise intervention or usual care. Prior to beginning aromatase inhibitor (AI) therapy, participants complete baseline assessments of cognitive function, cardiorespiratory fitness, blood-based biomarkers, physical activity and sleep, and symptoms (fatigue, sleep problems, depressive symptoms, anxiety). A random subset of participants (n = 150) undergoes neuroimaging procedures that include structural and functional magnetic resonance imaging assessments. All participants maintain an activity diary; physical activity and sleep monitoring is repeated three and seven months post-randomization. The remaining baseline assessments are repeated seven months post-randomization. If successful, exercise could be a low-cost method to improve cognitive function in women with breast cancer that is easily adaptable to the home or community. TRIAL REGISTRATION: Clinicaltrials.govNCT02793921. Registered 20 May 2016.

Trajectories of Cognitive Function and Associated Phenotypic and Genotypic Factors in Breast Cancer.

OBJECTIVES: This study identified women with unique trajectories of executive function, concentration, and visual working memory before and during adjuvant therapy for breast cancer, and examined phenotypic and genotypic predictors associated with subgroups. SAMPLE & SETTING: 399 postmenopausal women, of whom 288 were women with early-stage breast cancer and 111 were women without breast cancer, matched on age and years of education to the women with breast cancer, and all at an urban cancer center. METHODS & VARIABLES: A repeated-measures design was used; assessments occurred before adjuvant therapy and every six months post-therapy initiation. Group-based trajectory modeling determined subgroups. Multinomial logistic regression identified phenotypic and genotypic characteristics. RESULTS: Three executive function and concentration trajectory subgroups were identified. IMPLICATIONS FOR NURSING: Advancing age, greater pretherapy fatigue, and poorer pretherapy cognitive function are associated with the low subgroups. DNA repair and oxidative stress mechanisms may be involved in the cognitive changes that women experience.

Development of a Standardized Approach to Disclosing Amyloid Imaging Research Results in Mild Cognitive Impairment.

The increased use of PET amyloid imaging in clinical research has sparked numerous concerns about whether and how to return such research test results to study participants. Chief among these is the question of how best to disclose amyloid imaging research results to individuals who have cognitive symptoms that could impede comprehension of the information conveyed. We systematically developed and evaluated informational materials for use in pre-test counseling and post-test disclosures of amyloid imaging research results in mild cognitive impairment (MCI). Using simulated sessions, persons with MCI and their family care partners (N = 10 dyads) received fictitious but realistic information regarding brain amyloid status, followed by an explanation of how results impact Alzheimer's disease risk. Satisfaction surveys, comprehension assessments, and focus group data were analyzed to evaluate the materials developed. The majority of persons with MCI and their care partners comprehended and were highly satisfied with the information presented. Focus group data reinforced findings of high satisfaction and included 6 recommendations for practice: 1) offer pre-test counseling, 2) use clear graphics, 3) review participants' own brain images during disclosures, 4) offer take-home materials, 5) call participants post-disclosure to address emerging questions, and 6) communicate seamlessly with primary care providers. Further analysis of focus group data revealed that participants understood the limitations of amyloid imaging, but nevertheless viewed the prospect of learning one's amyloid status as valuable and empowering.

A New Measure of Research Participant Burden: Brief Report.

Effective conceptualizations of research burden should address indirect burdens related to research duration, intensity, and invasiveness. Introducing the concept of perceived research burden, we developed, tested, and validated a new instrument, the Perceived Research Burden Assessment (PeRBA). Initial psychometric evaluation of PeRBA reveals good internal consistency, evidence of face validity, and acceptable convergent and discriminant validity.

Influence of patient and treatment factors on adherence to adjuvant endocrine therapy in breast cancer.

PURPOSE/OBJECTIVES: To comprehensively assess the patient and illness or treatment factors that may predict nonadherence to adjuvant endocrine therapy and to explore whether an interaction occurs between these factors in women with breast cancer. DESIGN: Repeated-measures design. SETTING: The Outpatient Services of the Women's Cancer Program at the University of Pittsburgh Cancer Institute and participants' homes. SAMPLE: 91 women with early-stage breast cancer who received endocrine therapy. METHODS: Adherence was assessed continuously for the first 18 months of endocrine therapy. Patient and illness or treatment factors were assessed at four time points (Time 1 to Time 4). Time 1 (baseline) was within two weeks prior to the initiation of endocrine therapy. Times 2-4 occurred at six-month intervals, as many as 18 months after Time 1. MAIN RESEARCH VARIABLES: Adherence, patient factors, and illness or treatment factors. FINDINGS: Adherence to endocrine therapy declined significantly during the first 18 months of treatment in women with breast cancer. The presence of negative mood and symptoms before starting treatment predicted nonadherence to endocrine therapy over time. Perceptions of financial hardship, symptoms, disease stage, and more complex medication regimens intensified the effect of negative mood on adherence over time. CONCLUSIONS: Women with breast cancer may be at risk for nonadherence to prescribed endocrine therapy if they experience depression or anxiety and symptoms prior to initiating therapy. IMPLICATIONS FOR NURSING: Oncology nurses should be alert to women with breast cancer who are depressed or anxious or who are experiencing symptoms. Management of negative mood and symptoms may result in better adherence.

A Descriptive, Retrospective Study of After-hours Calls in Hospice and Palliative Care.

AIMS: Few studies have described after-hours calls in hospice patient care. This retrospective study examines the timing of after-hours telephone triage services; the reasons for access to after-hours hospice and palliative care services; and the predominant nursing interventions offered in after-hours calls in hospice and palliative care. METHODS: A fixed coding scheme was used to code a de-identified after-hours triage phone log of all calls between July 2005 and June 2006 (n=4,434) from a Pennsylvania hospice and palliative care services organization. Descriptive statistics were used to identify call timing pattern, call reasons, and predominant nursing interventions. RESULTS: Triage services were utilized most frequently to request assistance with signs and symptoms control (25.7%), report death (17.8%), and to request a home visit (15.3%). The top nursing interventions included updating case managers or supervisors about the needs of follow-up (29.5%), coordinating home visits (20.5%), and instructing caregivers or patients on how to control new signs and symptoms (19.8%). CONCLUSIONS: A better understanding of when and why patients and their family caregivers utilize after-hours hospice triage services can assist in the design of future proactive interventions to improve care, and enhance training for new and existing hospice triage nurses.

Pesticide safety behaviors in Latino farmworker family households.

BACKGROUND: Studies to assess pesticide exposure of individuals living in agricultural settings suggest that farmworkers create a "take-home" pathway from the fields to the home that increases exposure risk for non-farmworker household members. METHODS: A survey was conducted with 142 Latino women in farmworker family households in North Carolina to identify predictors of adherence to pesticide safety behaviors that may affect take-home exposure risk. Behaviors included changing work clothes before entering the house, storing and washing contaminated work clothes separately from family clothing, and showering upon returning home. RESULTS: The number of farmworkers in the household was negatively associated with adherence to recommended changing, storing, and showering behaviors. Most workers followed recommended laundry procedures for work clothes. CONCLUSIONS: Results support existing evidence for a take-home pathway for pesticide residues in homes with several farmworkers. Pesticide safety education needs to reinforce behaviors that reduce take-home exposure in farmworker households.