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Background Sedentary behavior is pervasive, especially in older adults, and is associated with cardiometabolic disease and mortality. Relationships between cardiometabolic biomarkers and sitting time are unexplored in older women, as are possible ethnic differences. Methods and Results Ethnic differences in sitting behavior and associations with cardiometabolic risk were explored in overweight/obese postmenopausal women (n=518; mean±SD age 63±6 years; mean body mass index 31.4±4.8 kg/m2). Accelerometer data were processed using validated machine-learned algorithms to measure total daily sitting time and mean sitting bout duration (an indicator of sitting behavior pattern). Multivariable linear regression was used to compare sitting among Hispanic women (n=102) and non-Hispanic women (n=416) and tested associations with cardiometabolic risk biomarkers. Hispanic women sat, on average, 50.3 minutes less/day than non-Hispanic women (P

BackgroundFor breast cancer survivors, moderate to vigorous physical activity (MVPA) is associated with improved survival. Less is known about the interrelationships of daytime activities (sedentary behavior [SB], light-intensity physical activity, and MVPA) and associations with survivors' health outcomes. This study will use isotemporal substitution to explore reallocations of time spent in daytime activities and associations with cancer recurrence biomarkers.MethodsBreast cancer survivors (N = 333; mean age 63 y) wore accelerometers and provided fasting blood samples. Linear regression models estimated the associations between daytime activities and cancer recurrence biomarkers. Isotemporal substitution models estimated cross-sectional associations with biomarkers when time was reallocated from of one activity to another. Models were adjusted for wear time, demographics, lifestyle factors, and medical conditions.ResultsMVPA was significantly associated with lower insulin, C-reactive protein, homeostatic model assessment of insulin resistance, and glucose, and higher sex hormone-binding globulin (all P < .05). Light-intensity physical activity and SB were associated with insulin and homeostatic model assessment of insulin resistance (both P < .05). Reallocating 18 minutes of SB to MVPA resulted in significant beneficial associations with insulin (-9.3%), homeostatic model assessment of insulin resistance (-10.8%), glucose (-1.7%), and sex hormone-binding globulin (7.7%). There were no significant associations when 79 minutes of SB were shifted to light-intensity physical activity.ConclusionsResults illuminate the possible benefits for breast cancer survivors of replacing time spent in SB with MVPA.

BackgroundEmerging 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.ObjectiveThe 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.MethodsA 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.ResultsParticipants 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.ConclusionsPhysical 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 registrationClinicalTrials.gov NCT02332876; https://clinicaltrials.gov/ct2/show/NCT02332876.

ObjectiveBreast cancer survivors experience problems with cognition that interfere with daily life and can last for years. In the general population, obesity and diabetes are risk factors for cognitive decline, and weight loss can improve cognition; however, the impact of intentional weight loss on cancer survivors' cognition has not been tested. We investigated the impact of weight loss and metformin on changes in cognitive function in a sample of breast cancer survivors.MethodsOverweight/obese postmenopausal breast cancer survivors (n = 333) were randomized to a weight loss intervention versus control and metformin versus placebo in a 2 × 2 factorial design. Outcomes were changes in five cognitive domains from baseline to 6 months measured by objective neurocognitive tests.ResultsThere were no statistically significant intervention effects for the metformin or weight loss interventions in five neurocognitive domains. Baseline body mass index (BMI) was a significant effect modifier of the changes in verbal functioning for the weight loss (P = 0.009) and metformin interventions (P = 0.0125). These effect modifications were independent of percent weight loss achieved during the 6-month study period.ConclusionsThis randomized controlled trial of weight loss and metformin interventions that examined changes to cognition among breast cancer survivors suggests that these interventions may not improve cognitive functioning among breast cancer survivors in general. However, weight loss may improve verbal functioning among individuals with a higher BMI.

Objectives: We aimed to quantify the agreement between self-report, standard cut-point accelerometer, and machine learning accelerometer estimates of physical activity (PA), and exam- ine how agreement changes over time among older adults in an intervention setting. Methods: Data were from a randomized weight loss trial that encouraged increased PA among 333 postmenopausal breast cancer survivors. PA was estimated using accelerometry and a validated questionnaire at baseline and 6-months. Accelerometer data were processed using standard cut-points and a validated machine learning algorithm. Agreement of PA at each time-point and change was assessed using mixed effects regression models and concordance correlation. Results: At baseline, self-report and machine learning provided similar PA estimates (mean dif- ference = 11.5 min/day) unlike self-report and standard cut-points (mean difference = 36.3 min/ day). Cut-point and machine learning methods assessed PA change over time more similarly than other comparisons. Specifically, the mean difference of PA change for the cut-point versus machine learning methods was 5.1 min/day for intervention group and 2.9 in controls, whereas it was ≥ 24.7 min/day for other comparisons. Conclusions: Intervention researchers are facing the issue of self-report measures introducing bias and accelerometer cut-points being insensi- tive. Machine learning approaches may bridge this gap.

Background:This study investigated the effects of metformin and weight loss on biomarkers associated with breast cancer prognosis. Methods:Overweight/obese postmenopausal breast cancer survivors (n = 333) were randomly assigned to metformin vs placebo and to a weight loss intervention vs control (ie, usual care). The 2 × 2 factorial design allows a single randomized trial to investigate the effect of two factors and interactions between them. Outcomes were changes in fasting insulin, glucose, C-reactive protein (CRP), estradiol, testosterone, and sex-hormone binding globulin (SHBG). The trial was powered for a main effects analysis of metformin vs placebo and weight loss vs control. All tests of statistical significance were two-sided. Results:A total of 313 women (94.0%) completed the six-month trial. High prescription adherence (ie, ≥80% of pills taken) ranged from 65.9% of participants in the metformin group to 81.3% of those in the placebo group (P < .002). Mean percent weight loss was statistically significantly higher in the weight loss group (-5.5%, 95% confidence interval [CI] = -6.3% to -4.8%) compared with the control group (-2.7%, 95% CI = -3.5% to -1.9%). Statistically significant group differences (ie, percent change in metformin group minus placebo group) were -7.9% (95% CI = -15.0% to -0.8%) for insulin, -10.0% (95% CI = -18.5% to -1.5%) for estradiol, -9.5% (95% CI = -15.2% to -3.8%) for testosterone, and 7.5% (95% CI = 2.4% to 12.6%) for SHBG. Statistically significant group differences (ie, percent change in weight loss group minus placebo group) were -12.5% (95% CI = -19.6% to -5.3%) for insulin and 5.3% (95% CI = 0.2% to 10.4%) for SHBG. Conclusions:As adjuvant therapy, weight loss and metformin were found to be a safe combination strategy that modestly lowered estrogen levels and advantageously affected other biomarkers thought to be on the pathway for reducing breast cancer recurrence and mortality.

BackgroundSedentary behavior is associated with increased risk of poor outcomes in breast cancer survivors, but underlying mechanisms are not well understood. This pilot study explored associations between different aspects of sedentary behaviors (sitting, prolonged sitting, sit-to-stand transitions, and standing) and breast cancer risk-related biomarkers in breast cancer survivors (n = 30).MethodsSedentary behavior variables were objectively measured with thigh-worn activPALs. Breast cancer risk-related biomarkers assessed were C-reactive protein (CRP), insulin, and homeostatic model assessment of insulin resistance (HOMA-IR) and were measured in fasting plasma samples. Linear regression models were used to investigate associations between sedentary behavior variables and biomarkers (log CRP, insulin, and HOMA-IR).ResultsSit-to-stand transitions were significantly associated with insulin resistance biomarkers (P  .05).ConclusionsSit-to-stand transitions may be an intervention target for reducing insulin resistance in breast cancer survivors, which may have favorable downstream effects on cancer prognosis.

BackgroundIncreasing 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.MethodsSedentary 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.ResultsOn 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 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.ConclusionsThe 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.

PurposeThis study examined relationships between sedentary behavior accumulated in different bout durations and quality of life (QoL) among breast cancer survivors.MethodsPostmenopausal breast cancer survivors completed the Short Form Health Survey to assess QoL and wore an accelerometer to measure sedentary behavior and physical activity between August 2011 and May 2013.ResultsParticipants (n = 134) averaged 509.7 min/day in sedentary time with 285.2 min/day in short bouts (

Purpose: To examine associations of prediagnosis high-sensitivity C-reactive protein (hsCRP) with breast cancer incidence and postdiagnosis survival and to assess whether associations are modified by body mass index (BMI).Methods: A prospective analysis of the Women's Health Initiative was conducted among 17,841 cancer-free postmenopausal women with baseline hsCRP measurements. Cox proportional hazards models were used to examine associations between hsCRP concentrations and (i) breast cancer risk (n cases = 1,114) and (ii) all-cause mortality after breast cancer diagnosis. HRs are per 1 SD in log hsCRP.Results: hsCRP was not associated with breast cancer risk overall [HR = 1.05; 95% confidence interval (CI), 0.98-1.12]; however, an interaction between BMI and hsCRP was observed (Pinteraction = 0.02). A 1 SD increase in log hsCRP was associated with 17% increased breast cancer risk (HR = 1.17; 95% CI, 1.03-1.33) among lean women (BMI < 25), whereas no association was observed among overweight/obese (BMI ≥ 25) women. Prediagnosis hsCRP was not associated with overall mortality (HR, 1.04; 95% CI, 0.88-1.21) after breast cancer diagnosis; however, an increased mortality risk was apparent among leaner women with higher hsCRP levels (HR, 1.39, 95% CI, 1.03-1.88).Conclusions: Prediagnosis hsCRP levels are not associated with postmenopausal breast cancer incidence or survival overall; however, increased risks are suggested among leaner women. The observed effect modification is in the opposite direction of a previous case-control study finding and warrants further investigation.Impact: Associations of higher CRP levels with incident breast cancer and survival after breast cancer may depend on BMI. Cancer Epidemiol Biomarkers Prev; 26(7); 1100-6. ©2017 AACR.

Background: Environmental factors may influence breast cancer; however, most studies have measured environmental exposure in neighborhoods around home residences (static exposure). We hypothesize that tracking environmental exposures over time and space (dynamic exposure) is key to assessing total exposure. This study compares breast cancer survivors' exposure to walkable and recreation-promoting environments using dynamic Global Positioning System (GPS) and static home-based measures of exposure in relation to insulin resistance.Methods: GPS data from 249 breast cancer survivors living in San Diego County were collected for one week along with fasting blood draw. Exposure to recreation spaces and walkability was measured for each woman's home address within an 800 m buffer (static), and using a kernel density weight of GPS tracks (dynamic). Participants' exposure estimates were related to insulin resistance (using the homeostatic model assessment of insulin resistance, HOMA-IR) controlled by age and body mass index (BMI) in linear regression models.Results: The dynamic measurement method resulted in greater variability in built environment exposure values than did the static method. Regression results showed no association between HOMA-IR and home-based, static measures of walkability and recreation area exposure. GPS-based dynamic measures of both walkability and recreation area were significantly associated with lower HOMA-IR (P < 0.05).Conclusions: Dynamic exposure measurements may provide important evidence for community- and individual-level interventions that can address cancer risk inequities arising from environments wherein breast cancer survivors live and engage.Impact: This is the first study to compare associations of dynamic versus static built environment exposure measures with insulin outcomes in breast cancer survivors. Cancer Epidemiol Biomarkers Prev; 26(7); 1078-84. ©2017 AACR.

PurposeTo examine whether baseline sleep duration or changes in sleep duration are associated with breast cancer prognosis among early-stage breast cancer survivors in the multi-center Women's Healthy Eating and Living Study.MethodsData were collected from 1995 to 2010. Analysis included 3047 women. Sleep duration was self-reported at baseline and follow-up intervals. Cox proportional hazard models were used to investigate whether baseline sleep duration was associated with breast cancer recurrence, breast cancer-specific mortality, and all-cause mortality. Time-varying models investigated whether changes in sleep duration were associated with breast cancer prognosis.ResultsCompared to women who slept 7-8 h/night at baseline, sleeping ≥9 h/night was associated with a 48% increased risk of breast cancer recurrence (Hazard ratio [HR] 1.48, 95% Confidence interval [CI] 1.01, 2.00), a 52% increased risk of breast cancer-specific mortality (HR 1.52, 95% CI 1.09, 2.13), and a 43% greater risk of all-cause mortality (HR 1.43, 95% CI 1.07, 1.92). Time-varying models showed analogous increased risk in those who inconsistently slept ≥9 h/night (all P

BackgroundMenopause is associated with significant hormonal changes that result in increased total body fat and abdominal fat, amplifying the risk for metabolic syndrome and diseases such as diabetes, cardiovascular disease and cancer in postmenopausal women. Intermittent fasting regimens hold significant health benefit promise for obese humans, however, regimens that include extreme daytime calorie restriction or daytime fasting are generally associated with hunger and irritability, hampering long-term compliance and adoption in the clinical setting. Time-restricted feeding (TRF), a regimen allowing eating only during a specific period in the normal circadian feeding cycle, without calorie restriction, may increase compliance and provide a more clinically viable method for reducing the detrimental metabolic consequences associated with obesity.MethodsWe tested TRF as an intervention in a mouse model of postmenopausal obesity. Metabolic parameters were measured using Clinical Laboratory Animal Monitoring System (CLAMS) and we carried out glucose tolerance tests. We also stained liver sections with oil red O to examine steatosis and measured gene expression related to gluconeogenesis.ResultsPreexisting metabolic disease was significantly attenuated during 7 weeks of TRF. Despite having access to the same high fat diet (HFD) as ad libitum fed (ALF) mice, TRF mice experienced rapid weight loss followed by a delayed improvement in insulin resistance and a reduced severity of hepatic steatosis by having access to the HFD for only 8h during their normal nocturnal feeding period. The lower respiratory exchange ratio in the TRF group compared with the ALF group early in the dark phase suggested that fat was the predominant fuel source in the TRF group and correlated with gene expression analyses that suggested a switch from gluconeogenesis to ketogenesis. In addition, TRF mice were more physically active than ALF fed mice.ConclusionsOur data support further analysis of TRF as a clinically viable form of intermittent fasting to improve metabolic health due to obesity.

Excess weight and physical inactivity are modifiable risk factors for breast cancer. Behavioral intervention is particularly important among women with an elevated risk profile. This trial tested an intervention that trained women to use a self-monitoring website to increase activity and lose weight. Women with BMI ≥27.5 kg/m(2) at elevated breast cancer risk were randomized to the intervention (N = 71) or usual care (N = 34). The intervention group received telephone-based coaching and used web-based self-monitoring tools. At 6 months, significant weight loss was observed in the intervention group (4.7 % loss from starting weight; SD = 4.7 %) relative to usual care (0.4 % gain; SD = 3.0 %) (p

ImportanceRodent studies demonstrate that prolonged fasting during the sleep phase positively influences carcinogenesis and metabolic processes that are putatively associated with risk and prognosis of breast cancer. To our knowledge, no studies in humans have examined nightly fasting duration and cancer outcomes.ObjectiveTo investigate whether duration of nightly fasting predicted recurrence and mortality among women with early-stage breast cancer and, if so, whether it was associated with risk factors for poor outcomes, including glucoregulation (hemoglobin A1c), chronic inflammation (C-reactive protein), obesity, and sleep.Design, setting, and participantsData were collected from 2413 women with breast cancer but without diabetes mellitus who were aged 27 to 70 years at diagnosis and participated in the prospective Women's Healthy Eating and Living study between March 1, 1995, and May 3, 2007. Data analysis was conducted from May 18 to October 5, 2015.ExposuresNightly fasting duration was estimated from 24-hour dietary recalls collected at baseline, year 1, and year 4.Main outcomes and measuresClinical outcomes were invasive breast cancer recurrence and new primary breast tumors during a mean of 7.3 years of study follow-up as well as death from breast cancer or any cause during a mean of 11.4 years of surveillance. Baseline sleep duration was self-reported, and archived blood samples were used to assess concentrations of hemoglobin A1c and C-reactive protein.ResultsThe cohort of 2413 women (mean [SD] age, 52.4 [8.9] years) reported a mean (SD) fasting duration of 12.5 (1.7) hours per night. In repeated-measures Cox proportional hazards regression models, fasting less than 13 hours per night (lower 2 tertiles of nightly fasting distribution) was associated with an increase in the risk of breast cancer recurrence compared with fasting 13 or more hours per night (hazard ratio, 1.36; 95% CI, 1.05-1.76). Nightly fasting less than 13 hours was not associated with a statistically significant higher risk of breast cancer mortality (hazard ratio, 1.21; 95% CI, 0.91-1.60) or a statistically significant higher risk of all-cause mortality (hazard ratio, 1.22; 95% CI, 0.95-1.56). In multivariable linear regression models, each 2-hour increase in the nightly fasting duration was associated with significantly lower hemoglobin A1c levels (β = -0.37; 95% CI, -0.72 to -0.01) and a longer duration of nighttime sleep (β = 0.20; 95% CI, 0.14-0.26).Conclusions and relevanceProlonging the length of the nightly fasting interval may be a simple, nonpharmacologic strategy for reducing the risk of breast cancer recurrence. Improvements in glucoregulation and sleep may be mechanisms linking nightly fasting with breast cancer prognosis.

Lifestyle factors have been well studied in relation to breast cancer prognosis overall; however, associations of lifestyle and late outcomes (>5 years after diagnosis) have been much less studied, and no studies have focused on estrogen receptor-positive (ER+) breast cancer survivors, who may have high risk of late recurrence and mortality. We utilized a large prospective pooling study to evaluate the associations of lifestyle factors with late recurrence and all-cause mortality among 6,295 5-year ER+ Stage I-III breast cancer survivors. Pooled and harmonized data were available on clinical factors and lifestyle factors (pre- to post-diagnosis weight change, body mass index (BMI) (kg/m(2)), recreational physical activity, alcohol intake and smoking history), measured on average 2.1 years after diagnosis. Updated information for weight only was available. Study heterogeneity was evaluated by the Q-statistic. Multivariable Cox regression models were stratified by study. Adjusting for clinical factors and potential confounders, ≥ 10% weight gain and obesity (BMI, 30-34.99 and ≥ 35) were associated with increased risk of late recurrence (hazard ratios (95% confidence intervals): 1.24 (1.00-1.53), 1.40 (1.05-1.86) and 1.41 (1.02-1.93), respectively). Daily alcohol intake was associated with late recurrence, 1.28 (1.01-1.62). Physical activity was inversely associated with late all-cause mortality (0.81 (0.71-0.93) and 0.71 (0.61-0.82) for 4.9 to

Weight loss and metformin are hypothesized to improve breast cancer outcomes; however the joint impacts of these treatments have not been investigated. Reach for Health is a randomized trial using a 2 × 2 factorial design to investigate the effects of weight loss and metformin on biomarkers associated with breast cancer prognosis among overweight/obese postmenopausal breast cancer survivors. This paper describes the trial recruitment strategies, design, and baseline sample characteristics. Participants were randomized in equal numbers to (1) placebo, (2) metformin, (3) weight loss intervention and placebo, or (4) weight-loss intervention and metformin. The lifestyle intervention was a personalized, telephone-based program targeting a 7% weight-loss in the intervention arm. The metformin dose was 1500 mg/day. The duration of the intervention was 6 months. Main outcomes were biomarkers representing 3 metabolic systems putatively related to breast cancer mortality: glucoregulation, inflammation, and sex hormones. Between August 2011 and May 2015, we randomized 333 breast cancer survivors. Mass mailings from the California Cancer Registry were the most successful recruitment strategy with over 25,000 letters sent at a cost of $191 per randomized participant. At baseline, higher levels of obesity were significantly associated with worse sleep disturbance and impairment scores, lower levels of physical activity and higher levels of sedentary behavior, hypertension, hypercholesterolemia, and lower quality of life (p

The purpose of this study was to examine post-diagnosis BMI, very low physical activity, and comorbidities, as predictors of breast cancer-specific and all-cause mortality. Data from three female US breast cancer survivor cohorts were harmonized in the After Breast Cancer Pooling Project (n = 9513). Delayed entry Cox proportional hazards models were used to examine the impact of three post-diagnosis lifestyle factors: body mass index (BMI), select comorbidities (diabetes only, hypertension only, or both), and very low physical activity (defined as physical activity

BackgroundDirect-to-consumer trackers and devices have potential to enhance theory-based physical activity interventions by offering a simple and pleasant way to help participants self-monitor their behavior. A secondary benefit of these devices is the opportunity for investigators to objectively track adherence to physical activity goals across weeks or even months, rather than relying on self-report or a small number of accelerometry wear periods. The use of consumer trackers for continuous monitoring of adherence has considerable potential to enhance physical activity research, but few studies have been published in this rapidly developing area.ObjectiveThe objective of the study was to assess the trajectory of physical activity adherence across a 16-week self-monitoring intervention, as measured by the Fitbit tracker.MethodsParticipants were 25 overweight or obese, postmenopausal women enrolled in the intervention arm of a randomized controlled physical activity intervention trial. Each participant received a 16-week technology-based intervention that used the Fitbit physical activity tracker and website. The overall study goal was 150 minutes/week of moderate to vigorous intensity physical activity (MVPA) and 10,000 steps/day; however, goals were set individually for each participant and updated at Week 4 based on progress. Adherence data were collected by the Fitbit and aggregated by Fitabase. Participants also wore an ActiGraph GT3X+ accelerometer for 7 days prior to the intervention and again during Week 16.ResultsThe median participant logged 10 hours or more/day of Fitbit wear on 95% of the 112 intervention days, with no significant decline in wear over the study period. Participants averaged 7540 (SD 2373) steps/day and 82 minutes/week (SD 43) of accumulated "fairly active" and "very active" minutes during the intervention. At Week 4, 80% (20/25) of women chose to maintain/increase their individual MVPA goal and 72% (18/25) of participants chose to maintain/increase their step goal. Physical activity levels were relatively stable after peaking at 3 weeks, with only small declines of 8% for steps (P=.06) and 14% for MVPA (P=.05) by 16 weeks.ConclusionsThese data indicate that a sophisticated, direct-to-consumer activity tracker encouraged high levels of self-monitoring that were sustained over 16 weeks. Further study is needed to determine how to motivate additional gains in physical activity and evaluate the long-term utility of the Fitbit tracker as part of a strategy for chronic disease prevention.Trial registrationClinicaltrials.gov NCT01837147; http://clinicaltrials.gov/ct2/show/NCT01837147 (Archived by WebCite at http://www.webcitation.org/6d0VeQpvB).

IntroductionMany breast cancer survivors experience problems with cognitive functioning that can persist years after treatment. Increasing physical activity has been shown to improve cognitive functioning in healthy and cognitively impaired adults, but has not yet been tested in cancer survivors. The primary aim of this randomized controlled trial is to examine the effects of a 3-month physical activity intervention compared to a waitlist Control arm on neuropsychological outcomes and subjective cognitive concerns in breast cancer survivors.MethodsEighty sedentary breast cancer survivors, self-reporting difficulties with cognition, will be randomized into an Exercise arm or Control arm. The Exercise arm includes an activity tracker (i.e., a Fitbit), phone calls, plus tailored and non-tailored email content. The Control arm will receive emails on women's health topics on the same schedule as the Exercise arm. Assessments conducted at baseline and 3 months include: neuropsychological testing, cognitive concerns and other aspects of quality of life, and 7 days of a hip-worn accelerometer. Participants will also provide fasting blood draws to assess brain-derived neurotropic factor, Insulin-like growth factor 1, insulin resistance, and C-reactive protein. Primary and secondary outcomes are changes in neuropsychological testing and cognitive concerns. Biomarkers will be examined to further understand the underlying relationship between physical activity and cognition.ConclusionThe Memory & Motion study is designed to test whether increasing physical activity can improve cognitive functioning in breast cancer survivors. Results from this study could be used to guide development of interventions to improve cognitive functioning in breast cancer survivors.

PurposeThis study aimed to explore the relationship between objectively measured physical activity and cognitive functioning in breast cancer survivors.MethodsParticipants were 136 postmenopausal breast cancer survivors. Cognitive functioning was assessed using a comprehensive computerized neuropsychological test. Seven-day physical activity was assessed using hip-worn accelerometers. Linear regression models examined associations of minutes per day of physical activity at various intensities on individual cognitive functioning domains. The partially adjusted model controlled for primary confounders (model 1), and subsequent adjustments were made for chemotherapy history (model 2) and body mass index (BMI) (model 3). Interaction and stratified models examined BMI as an effect modifier.ResultsModerate-to-vigorous physical activity (MVPA) was associated with information processing speed. Specifically, 10 min of MVPA was associated with a 1.35-point higher score (out of 100) on the information processing speed domain in the partially adjusted model and a 1.29-point higher score when chemotherapy was added to the model (both p

ObjectiveWeight, physical activity, and sleep are modifiable lifestyle factors that impact cognitive functioning in noncancer populations but have yet to be examined in cancer survivors. The aim of the study was to assess the relationship of obesity, physical activity, and sleep, with cognitive functioning among breast cancer survivors.MethodsParticipants were 136 early-stage postmenopausal breast cancer survivors who completed an assessment of neuropsychological testing, height, weight, physical activity, and sleep. Linear regression models examined the associations of the seven neuropsychological domains with obesity, physical activity, and sleep. Logistic regression models examined odd of impairment in each domain. All models controlled for breast cancer treatment variables and relevant demographic and clinical variables.ResultsObese participants had significantly worse performance (β = -5.04, standard error (SE) = 2.53) and were almost three times more likely to be impaired (odds ratio (OR) = 2.87; 95% CI: 1.02-8.10) on the Information processing domain. The highest tertile of physical activity was significantly related to better performance on the executive functioning domain (β = 5.13, SE = 2.42) and attention domain (β = 4.26, SE = 2.07). The middle tertile of physical activity was significantly related to better performance (β = 9.00, SE = 3.09) and decreased odds of impairment (OR = 0.89, 95% CI: 0.07-0.91) on the visual-spatial domain. More hours of sleep per night was significantly associated with better performance (β = 2.69, SE = 0.98) and decreased odds of impairment (OR = 0.52; 95% CI: 0.33-0.82) on the verbal functioning domain.ConclusionsThese findings suggest that obesity, physical activity, and sleep are related to cognitive functioning among breast cancer survivors and have potential to be intervention targets to improve cognitive functioning.

BackgroundA novel line of research has emerged, suggesting that daily feeding-fasting schedules that are synchronized with sleep-wake cycles have metabolic implications that are highly relevant to breast cancer. We examined associations of nighttime fasting duration with biomarkers of breast cancer risk among women in the 2009-2010 U.S. National Health and Nutrition Examination Survey.MethodsDietary, anthropometric, and HbA1c data were available for 2,212 women, and 2-hour postprandial glucose concentrations were available for 1,066 women. Nighttime fasting duration was calculated using 24-hour food records. Separate linear regression models examined associations of nighttime fasting with HbA1c and 2-hour glucose concentrations. Logistic regression modeled associations of nighttime fasting with elevated HbA1c (HbA1c ≥ 39 mmol/mol or 5.7%) and elevated 2-hour glucose (glucose ≥ 140 mg/dL). All models adjusted for age, education, race/ethnicity, body mass index, total kcal intake, evening kcal intake, and the number of eating episodes per day.ResultsEach 3-hour increase in nighttime fasting (roughly 1 SD) was associated with a 4% lower 2-hour glucose measurement [β, 0.96; 95% confidence interval (CI), 0.93-1.00; P < 0.05], and a nonstatistically significant decrease in HbA1c. Logistic regression models indicate that each 3-hour increase in nighttime fasting duration was associated with roughly a 20% reduced odds of elevated HbA1c (OR, 0.81; 95% CI, 0.68-0.97; P < 0.05) and nonsignificantly reduced odds of elevated 2-hour glucose.ConclusionsA longer nighttime duration was significantly associated with improved glycemic regulation.ImpactRandomized trials are needed to confirm whether prolonged nighttime fasting could improve biomarkers of glucose control, thereby reducing breast cancer risk.

ObjectivesTo determine whether statin treatment is associated with increased risk of haemorrhagic stroke (HS) in older women. A secondary objective was to evaluate HS risk in users of combined statin and antiplatelet treatment.DesignObservational study: secondary data analysis from the Women's Health Initiative (WHI) clinical trials.SettingWomen were recruited from 40 participating sites.ParticipantsCohort of 68,132 women followed through 2005 (parent study) and for an additional 5 years in the extension study.Main outcome measuresStatin use was assessed at baseline and at follow-up visits (1, 3, 6 and 9 years). Women brought medications in original containers for inventory. Strokes were ascertained semiannually and centrally adjudicated. Risk of HS by statin use (time-varying covariate, with the 'no use' category as the referent) was estimated from Cox proportional hazard regression models adjusted for age (model 1); risk factors for HS (model 2); and possible confounders by indication (model 3). Prespecified subgroup analyses were conducted by use of antiplatelet medications.ResultsFinal models included 67,882 women (mean age, 63±7 years). Over a mean follow-up of 12 years, incidence rates of HS were 6.4/10,000 person-years among statin users and 5.0/10,000 person-years among non-users (p=0.11). The unadjusted risk of HS in statin users was 1.21 (CI 0.96 to 1.53); after adjusting for age and HS risk factors the HR was 0.98 (CI 0.76 to 1.26). Risk of HS was higher among women on statins and antiplatelet agents versus women on antiplatelet medications alone (HR=1.59; CI 1.03 to 2.47); p for interaction=0.011.ConclusionsThis retrospective analysis did not show an association between statin use and HS risk among older women. HS risk was higher among women taking statins with antiplatelet agents. These findings warrant further investigation, given potential implications for clinical decision-making.

Emerging evidence suggests that there is interplay between the frequency and circadian timing of eating and metabolic health. We examined the associations of eating frequency and timing with metabolic and inflammatory biomarkers putatively associated with breast cancer risk in women participating in the National Health and Nutrition Examination 2009-2010 Survey. Eating frequency and timing variables were calculated from 24-hour food records and included (1) proportion of calories consumed in the evening (5 pm-midnight), (2) number of eating episodes per day, and (3) nighttime fasting duration. Linear regression models examined each eating frequency and timing exposure variable with C-reactive protein (CRP) concentrations and the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Each 10 percent increase in the proportion of calories consumed in the evening was associated with a 3 percent increase in CRP. Conversely, eating one additional meal or snack per day was associated with an 8 percent reduction in CRP. There was a significant interaction between proportion of calories consumed in the evening and fasting duration with CRP (p = 0.02). A longer nighttime fasting duration was associated with an 8 percent lower CRP only among women who ate less than 30% of their total daily calories in the evening (p = 0.01). None of the eating frequency and timing variables were significantly associated with HOMA-IR. These findings suggest that eating more frequently, reducing evening energy intake, and fasting for longer nightly intervals may lower systemic inflammation and subsequently reduce breast cancer risk. Randomized trials are needed to validate these associations.

PurposeLow physical functioning among breast cancer survivors appears to reduce survival, although the mechanisms underlying these associations are not clear. We examined inflammation as a possible biological mediator of association between low physical functioning and mortality after breast cancer.MethodsAnalysis included 2,892 participants from the Women's Healthy Eating and Living Study. All measures were collected at study baseline. Physical function was assessed by the Short Form 36 (SF-36) Health Survey Physical Function subscale. Low physical function was defined as the bottom tertile of the subscale score. Inflammation was measured as serum concentration of C-reactive protein (CRP). Cox proportional hazards modeled the associations of low physical function and the putative mediator (i.e., CRP) with all-cause and breast cancer-specific mortality.ResultsThere were 293 deaths during study follow up, with 243 due to breast cancer. Low physical functioning was associated with a 50 % higher risk of all-cause mortality (HR, 1.49; 95 % CI, 1.2-1.9) and a 40 % higher risk of breast cancer-specific mortality (HR, 1.39; 95 % CI, 1.1-1.8), after adjustment for covariates. The addition of CRP did not markedly change the all-cause mortality hazard ratio attributed to low physical functioning. However, the addition of CRP modestly attenuated the breast cancer-specific mortality hazard ratio such that it was no longer statistically significant.ConclusionsInterventions to improve physical functioning may prevent early morbidity and mortality among breast cancer survivors.Implications for cancer survivorsFunctional status measure may be a valuable indicator of long-term health outcomes among breast cancer survivors.

BackgroundThe insulin-like growth factor-I (IGFI) receptor is a potential target for breast cancer treatment and may be influenced by dietary intake.MethodsNested, case-control study of 265 postmenopausal breast cancer survivors; primary breast cancer tissue was stained to determine IGFI receptor status. Change in carbohydrate intake from baseline to year 1 of study was estimated from 24-hour dietary recalls. Breast cancer recurrence cases (91) were matched to two controls (n = 174) on disease and study characteristics and counter matched on change in carbohydrate intake. Weighted conditional logistic regression models fit the risk of recurrence on IGFI receptor status and dietary change.ResultsHalf of the tumors were IGFI receptor positive. Increased risk of recurrence was associated with IGFI receptor-positive status [HR 1.7; 95% confidence interval (CI), 1.2-2.5] and, separately, with a stable/increased intake of carbohydrates (HR 2.0; 95% CI, 1.3-5.0). There was a borderline significant interaction between those two variables (P = 0.11). Specifically, carbohydrate intake had no significant impact on risk of recurrence among women who were receptor negative, yet increased the risk of recurrence by more than 5-fold among women who were receptor positive (HR 5.5; 95% CI, 1.8-16.3).ConclusionsAmong women whose tumor tissue is positive for the IGFI receptor, reducing carbohydrate intake after diagnosis could reduce the risk of breast cancer recurrence. These findings need replication in a larger sample.ImpactThis is the first study to suggest that it may be possible to personalize dietary recommendations for breast cancer survivors based on molecular characteristics of their primary tumor tissue. .

Habitual short sleep duration appears to increase the risk of obesity. The objective of this paper is to investigate the association of habitual sleep duration with objective measures of energy balance. One hundred twelve African-American and 111 non-Hispanic whites aged 21-69 y participated in a cross-sectional study of dietary assessment and biomarkers. Participants reported the mean number of hours per day spent sleeping over the past year. Short sleep duration was defined as ≤6 h/d of sleep. Energy intake (kilocalories) was objectively assessed using the 2-point doubly labeled water technique to determine total energy expenditure, which is approximately equal to energy intake. Physical activity energy expenditure (kilocalories) was estimated as total energy expenditure minus each participant's calculated basal metabolic rate and the thermogenic effect of food. Compared with participants who slept ≤6 h, individuals who slept 8 h were significantly less likely to be obese (OR: 0.33; 95% CI: 0.14, 0.79). However, this association was not linear across 6-9 h of sleep (P-trend = 0.16). There was an inverse association between sleep and energy intake (P-trend = 0.07): compared with ≤6 h/d, adults who reported ≥9 h sleep consumed 178 fewer kcal/d. There was also an inverse association between sleep and physical activity (P-trend = 0.05): compared with ≤6 h/d of sleep, adults who reported 9 h of usual sleep expended 113 fewer kcal/d in physical activity. These data indicate that, compared with longer sleep duration, adults who report habitual short sleep duration have somewhat higher physical activity energy expenditure but considerably higher energy intake. Habitual short sleep duration appears to be 1 of the facets of modern life leading to a mismatch between energy intake and physical activity.

BackgroundThere is controversy on whether former smokers have increased risk for breast cancer recurrence or all-cause mortality, regardless of how much they smoked.MethodsData were from three US cohorts in the After Breast Cancer Pooling Project, with detailed information on smoking among 9975 breast cancer survivors. Smoking was assessed an average of 2 years after diagnosis. Delayed entry Cox proportional hazards models were used to examine the relationships of smoking status, cigarettes per day, years of smoking, and pack years with breast cancer prognosis. Endpoints included breast cancer recurrence (n = 1727), breast cancer mortality (n = 1059), and overall mortality (n = 1803).ResultsCompared with never smokers, former smokers with less than 20 pack-years of exposure had no increased risk of any outcome. However, former smokers with 20 to less than 34.9 pack-years of exposure had a 22% increased risk of breast cancer recurrence (hazard ratio [HR] = 1.22; 95% confidence interval [CI] = 1.01 to 1.48) and a 26% increased risk of all-cause mortality (HR = 1.26; 95% CI = 1.07 to 1.48). For former smokers with 35 or more pack-years of exposure, the probability of recurrence increased by 37% (HR = 1.37; 95% CI = 1.13 to 1.66), breast cancer mortality increased by 54% (HR = 1.54; 95% CI = 1.24 to 1.91), and all-cause mortality increased by 68% (HR = 1.68; 95% CI = 1.44 to 1.96). Current smoking increased the probability of recurrence by 41% (HR = 1.41; 95% CI = 1.16 to 1.71), increased breast cancer mortality by 60% (HR = 1.61; 95% CI = 1.28 to 2.03), and doubled the risk of all-cause mortality (HR = 2.17; 95% CI = 1.85 to 2.54).ConclusionsLifetime cigarette smoking was statistically significantly associated with a poor prognosis among women diagnosed with breast cancer, dose-dependent increased risks of recurrence, and breast cancer and all-cause mortality.

BackgroundSerum C-reactive protein (CRP) is a marker of acute inflammatory response and has been associated with health outcomes in some studies. Inflammation and immune response may have potential prognostic implications for breast cancer survivors.MethodsThe Women's Healthy Eating and Living Study includes 2,919 early-stage breast cancer survivors with serum collected 2 years postdiagnosis and follow-up for clinical outcomes over approximately 7 years. CRP concentrations were measured using high-sensitivity electrochemiluminescence assay. Outcomes, including all-cause mortality, breast cancer-specific mortality, and additional breast cancer events were oncologist verified from medical records and death certificates. Cox proportional hazards models were conducted with adjustment for potential confounding factors to generate HRs and 95% confidence intervals (CI).ResultsCRP concentrations in women diagnosed with breast cancer were associated with death due to any cause, death due to breast cancer, and additional breast cancer events, after adjustment for sociodemographic and cancer characteristics (lnCRP: P < 0.05 for all three outcomes). The HR for women with (vs. without) acute inflammation suggests a threshold effect on overall survival, rather than a dose-response relationship (≥ 10.0 mg/L vs.

BackgroundAmong postmenopausal breast cancer survivors, poor physical health has been associated with higher risks of breast cancer events. Obesity and physical inactivity are known risk factors for poor physical health, while circulating estrogen is an additional potential risk factor. We tested the hypothesis that the relationship between poor physical health and worse breast cancer outcomes is mediated by higher estrogen concentrations associated with body size and physical inactivity.MethodsWe used data from 1030 postmenopausal breast cancer survivors to examine the association between serum estradiol levels, body mass index (BMI), physical activity, and RAND-36-item Health Survey (SF-36) physical health.ResultsIn univariate analysis, poor physical health was associated with higher estradiol levels, in addition to obesity and low physical activity. Higher estradiol levels were significantly associated with higher odds of poor physical health (odds ratio, OR, 1.20 [95% confidence interval 1.03-1.39]) in a multivariable model adjusting for age, cancer stage and treatment, alcohol use, and physical activity. However, the relationship between estradiol levels and poor physical health was no longer significant (OR 1.06 [0.91-1.24]) after adding BMI in the model. In multivariate analysis, only poor physical health resulted in higher risks of recurrence (hazard ratio 1.33 [95% CI 1.08-1.64]).ConclusionsThese findings indicate that estradiol is related to poor physical health, but is not an independent risk factor from body size or inactivity. While obesity and physical activity in survivorship are potential targets for improving physical health, other biological processes that impact physical health, e.g. inflammation, remain to be identified.

ObjectivesTo explore the relationship between cognitive functioning and time spent at different intensities of physical activity (PA) in free-living older adults.DesignCross sectional analyses.SettingContinuing care retirement communities.ParticipantsOlder adults residing in seven continuing care retirement communities in San Diego County with an average age of 83; 70% were female, and 35% had a graduate-level education (N = 217).MeasurementsPA was measured objectively using hip worn accelerometers with data aggregated to the minute level. Three cut points were used to assess low light-intensity PA (LLPA), high light-intensity PA (HLPA), and moderate- to vigorous-intensity PA (MVPA). The Trail Making Test (TMT) Parts A and B were completed, and time for each test (seconds) and time for Part B minus time for Part A (seconds) were used as measures of cognitive function. Variables were log-transformed and entered into linear regression models adjusting for demographic factors (age, education, sex) and other PA intensity variables.ResultsLLPA was not related to any TMT test score. HLPA was significantly related to TMT A, B, and B minus A but only in unadjusted models. MVPA was related to TMT B and B minus A after adjusting for demographic variables.ConclusionThere may be a dose response between PA intensity and cognitive functioning in older adults. The stronger findings supporting a relationship between MVPA and cognitive functioning are consistent with previous observational and intervention studies.

ObjectiveResearch suggests that physical activity is associated with improved breast cancer survival, yet no studies have examined the association between post-diagnosis changes in physical activity and breast cancer outcomes. The aim of this study was to determine whether baseline activity and 1-year change in activity are associated with breast cancer events or mortality.MethodsA total of 2,361 post-treatment breast cancer survivors (Stage I-III) enrolled in a randomized controlled trial of dietary change completed physical activity measures at baseline and one year. Physical activity variables (total, moderate-vigorous, and adherence to guidelines) were calculated for each time point. Median follow-up was 7.1 years. Outcomes were invasive breast cancer events and all-cause mortality.ResultsThose who were most active at baseline had a 53% lower mortality risk compared to the least active women (HR = 0.47; 95% CI: 0.26, 0.84; p = .01). Adherence to activity guidelines was associated with a 35% lower mortality risk (HR = 0.65, 95% CI: 0.47, 0.91; p < .01). Neither baseline nor 1-year change in activity was associated with additional breast cancer events.ConclusionsHigher baseline (post-treatment) physical activity was associated with improved survival. However, change in activity over the following year was not associated with outcomes. These data suggest that long-term physical activity levels are important for breast cancer prognosis.

BackgroundMillions of postmenopausal women use multivitamins, often believing that supplements prevent chronic diseases such as cancer and cardiovascular disease (CVD). Therefore, we decided to examine associations between multivitamin use and risk of cancer, CVD, and mortality in postmenopausal women.MethodsThe study included 161 808 participants from the Women's Health Initiative clinical trials (N = 68 132 in 3 overlapping trials of hormone therapy, dietary modification, and calcium and vitamin D supplements) or an observational study (N = 93 676). Detailed data were collected on multivitamin use at baseline and follow-up time points. Study enrollment occurred between 1993 and 1998; the women were followed up for a median of 8.0 years in the clinical trials and 7.9 years in the observational study. Disease end points were collected through 2005. We documented cancers of the breast (invasive), colon/rectum, endometrium, kidney, bladder, stomach, ovary, and lung; CVD (myocardial infarction, stroke, and venous thromboembolism); and total mortality.ResultsA total of 41.5% of the participants used multivitamins. After a median of 8.0 years of follow-up in the clinical trial cohort and 7.9 years in the observational study cohort, 9619 cases of breast, colorectal, endometrial, renal, bladder, stomach, lung, or ovarian cancer; 8751 CVD events; and 9865 deaths were reported. Multivariate-adjusted analyses revealed no association of multivitamin use with risk of cancer (hazard ratio [HR], 0.98, and 95% confidence interval [CI], 0.91-1.05 for breast cancer; HR, 0.99, and 95% CI, 0.88-1.11 for colorectal cancer; HR, 1.05, and 95% CI, 0.90-1.21 for endometrial cancer; HR, 1.0, and 95% CI, 0.88-1.13 for lung cancer; and HR, 1.07, and 95% CI, 0.88-1.29 for ovarian cancer); CVD (HR, 0.96, and 95% CI, 0.89-1.03 for myocardial infarction; HR, 0.99, and 95% CI, 0.91-1.07 for stroke; and HR, 1.05, and 95% CI, 0.85-1.29 for venous thromboembolism); or mortality (HR, 1.02, and 95% CI, 0.97-1.07).ConclusionAfter a median follow-up of 8.0 and 7.9 years in the clinical trial and observational study cohorts, respectively, the Women's Health Initiative study provided convincing evidence that multivitamin use has little or no influence on the risk of common cancers, CVD, or total mortality in postmenopausal women.

BackgroundThe Women's Health Initiative (WHI) and other clinical trials indicate that significant health risks are associated with combination hormone use. Less is known about the effect of hormone therapy on health-related quality of life.MethodsThe WHI randomly assigned 16,608 postmenopausal women 50 to 79 years of age (mean, 63) with an intact uterus at base line to estrogen plus progestin (0.625 mg of conjugated equine estrogen plus 2.5 mg of medroxyprogesterone acetate, in 8506 women) or placebo (in 8102 women). Quality-of-life measures were collected at base line and at one year in all women and at three years in a subgroup of 1511 women.ResultsRandomization to estrogen plus progestin resulted in no significant effects on general health, vitality, mental health, depressive symptoms, or sexual satisfaction. The use of estrogen plus progestin was associated with a statistically significant but small and not clinically meaningful benefit in terms of sleep disturbance, physical functioning, and bodily pain after one year (the mean benefit in terms of sleep disturbance was 0.4 point on a 20-point scale, in terms of physical functioning 0.8 point on a 100-point scale, and in terms of pain 1.9 points on a 100-point scale). At three years, there were no significant benefits in terms of any quality-of-life outcomes. Among women 50 to 54 years of age with moderate-to-severe vasomotor symptoms at base line, estrogen and progestin improved vasomotor symptoms and resulted in a small benefit in terms of sleep disturbance but no benefit in terms of the other quality-of-life outcomes.ConclusionsIn this trial in postmenopausal women, estrogen plus progestin did not have a clinically meaningful effect on health-related quality of life.

Examined the impact of lifestyle on the effectiveness of a low-intensity dietary intervention. Analysis of data from the Eating Patterns Study indicated that people who practiced certain combinations of health behaviors responded differently to the low-intensity dietary intervention. People with high-risk behaviors were the least successful in changing their diet. (SM)