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.

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.

What do perceived cognitive problems reflect?

Women with breast cancer frequently report cognitive problems to healthcare providers during and after adjuvant therapy. Patients' perceptions of their cognitive problems would be expected to relate to objectively measured cognitive impairments. We explored the relationship between perceived cognitive function and objective ratings of thinking ability in early-stage breast cancer patients receiving hormonal therapy. In particular, we targeted objective measures of learning and memory as the primary endpoints in this exploratory study. We included a comprehensive battery of objective measures of cognitive function to explore relationships between perceived cognitive problems and impairments in other domains of cognitive function. At a minimum, our results indicated that women's complaints of cognitive problems should prompt additional assessment to clarify the bases of the problem and initiate appropriate intervention.

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.

Memory impairments with adjuvant anastrozole versus tamoxifen in women with early-stage breast cancer.

OBJECTIVE: Hormones have been implicated as modulators of cognitive functioning. For instance, results of our previous work in women with breast cancer showed that cognitive impairment was more severe and involved more memory domains in those who received adjuvant tamoxifen therapy compared with women who received chemotherapy alone or no adjuvant therapy. Recently aromatase inhibitors such as anastrozole have been used in lieu of tamoxifen for the adjuvant treatment of postmenopausal women with hormone receptor-positive, early-stage breast cancer. Plasma estrogen levels are significantly lower in women who receive anastrozole compared with those who receive tamoxifen. We hypothesized, therefore, that anastrozole would have a more profound effect on cognitive function than tamoxifen, a mixed estrogen agonist/antagonist. DESIGN: To test this hypothesis we compared cognitive function in women with early-stage breast cancer who received tamoxifen with those who received anastrozole therapy in a cross-sectional study. We evaluated cognitive function, depression, anxiety, and fatigue in 31 postmenopausal women with early-stage breast cancer who were between the ages of 21 and 65 years and treated with tamoxifen or anastrozole for a minimum of 3 months. RESULTS: The results showed that women who received anastrozole had poorer verbal and visual learning and memory than women who received tamoxifen. CONCLUSIONS: Additional, prospective studies are needed to validate and confirm the changes in cognitive function associated with hormone therapy for breast cancer.

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.