Associations between health-related fitness and patient-reported symptoms in newly diagnosed breast cancer patients.

BACKGROUND: Newly diagnosed breast cancer patients experience symptoms that may affect their quality of life, treatment outcomes, and survival. Preventing and managing breast cancer-related symptoms soon after diagnosis is essential. The purpose of this study was to investigate the associations between health-related fitness (HRF) and patient-reported symptoms in newly diagnosed breast cancer patients. METHODS: This study utilized baseline data from the Alberta Moving Beyond Breast Cancer Cohort Study that were collected within 90 days of diagnosis. HRF measures included peak cardiopulmonary fitness (peak volume of oxygen consumption (VO2peak)), maximal muscular strength and endurance, flexibility, and body composition. Symptom measures included depression, sleep quality, and fatigue. Adjusted multivariable logistic regression was performed for analyses. RESULTS: Of 1458 participants, 51.5% reported poor sleep quality, 26.5% reported significant fatigue, and 10.4% reported moderate depression. In multivariable-adjusted models, lower relative VO2peak was independently associated with a greater likelihood of all symptom measures, including moderate depression (p < 0.001), poor sleep quality (p = 0.009), significant fatigue (p = 0.008), any symptom (p < 0.001), and multiple symptoms (p < 0.001). VO2peak demonstrated threshold associations with all symptom measures such that all 3 lower quartiles exhibited similar elevated risk compared to the highest quartile. The strength of the threshold associations varied by the symptom measure with odds ratios ranging from ∼1.5 for poor sleep quality to ∼3.0 for moderate depression and multiple symptoms. Moreover, lower relative upper body muscular endurance was also independently associated with fatigue in a dose-response manner (p = 0.001), and higher body weight was independently associated with poor sleep quality in an inverted U pattern (p = 0.021). CONCLUSION: Relative VO2peak appears to be a critical HRF component associated with multiple patient-reported symptoms in newly diagnosed breast cancer patients. Other HRF parameters may also be important for specific symptoms. Exercise interventions targeting different HRF components may help newly diagnosed breast cancer patients manage specific symptoms and improve outcomes.

Prospective cohort of pre- and post-diagnosis alcohol consumption and cigarette smoking on survival outcomes: an Alberta Endometrial Cancer Cohort Study.

PURPOSE: To examine the independent and joint relationships between cigarette smoking and alcohol consumption with survival outcomes after endometrial cancer diagnosis. METHODS: Pre- and post-diagnosis smoking and drinking histories were obtained from endometrial cancer survivors diagnosed between 2002 and 2006 during in-person interviews at-diagnosis and at ~ 3 years post-diagnosis. Participants were followed until death or January 2022. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated with Cox proportional hazards regression for associations with disease-free survival (DFS) and overall survival (OS). RESULTS: During a median 16.9 years of follow-up (IQR = 15.5-18.1 years), 152 of the 540 participants had a DFS event (recurrence: n = 73; deaths: n = 79) and 134 died overall. Most participants in this cohort were current drinkers (pre = 61.3%; post = 64.7%) while few were current cigarette smokers (pre = 12.8%; post = 11.5%). Pre-diagnosis alcohol consumption was not associated with survival, yet post-diagnosis alcohol intake ≥ 2 drinks/week was associated with worse OS compared with lifetime abstention (HR = 2.36, 95%CI = 1.00-5.54) as well as light intake (HR = 3.87, 95% CI = 1.67-8.96). Increased/consistently high alcohol intake patterns were associated with worse OS (HR = 2.91, 95% CI = 1.15-7.37) compared with patterns of decreased/ceased intake patterns after diagnosis. A harmful dose-response relationship per each additional pre-diagnosis smoking pack-year with OS was noted among ever smokers. In this cohort, smoking and alcohol individually were not associated with DFS and combined pre-diagnosis smoking and alcohol intakes were not associated with either outcome. CONCLUSION: Endometrial cancer survivors with higher alcohol intakes after diagnosis had poorer OS compared with women who had limited exposure. Larger studies powered to investigate the individual and joint impacts of cigarette smoking and alcohol use patterns are warranted to provide additional clarity on these modifiable prognostic factors.

Updated systematic review of the effects of exercise on understudied health outcomes in cancer survivors.

INTRODUCTION: The American College of Sports Medicine provided guidelines for exercise prescriptions in cancer survivors for specific cancer- and treatment-related health outcomes. However, there was insufficient evidence to generate exercise prescriptions for 10 health outcomes of cancer treatment. We sought to update the state of evidence. METHODS: We conducted a systematic review of these 10 understudied health outcomes (bone health, sleep, cardiovascular function, chemotherapy-induced peripheral neuropathy (CIPN), cognitive function, falls and balance, nausea, pain, sexual function, and treatment tolerance) and provided an update of evidence. RESULTS: While the evidence base for each outcome has increased, there remains insufficient evidence to generate exercise prescriptions. Common limitations observed across outcomes included: variability in type and quality of outcome measurement tools, variability in definitions of the health outcomes, a lack of phase III trials, and a majority of trials investigating breast or prostate cancer survivors only. CONCLUSION: We identified progress in the field of exercise oncology for several understudied cancer- and treatment-related health outcomes. However, we were not able to generate exercise prescriptions due to continued insufficient evidence base. More work is needed to prescribe exercise as medicine for these understudied health outcomes, and our review highlights several strategies to aid in research acceleration within these areas of exercise oncology.

Social-cognitive, demographic, clinical, and health-related correlates of physical activity and sedentary behaviour in newly diagnosed women with breast cancer.

PURPOSE: Identifying correlates of physical activity and sedentary behaviour allows for the identification of factors that may be targeted in future behaviour change interventions. This study sought to determine the social-cognitive, demographic, clinical, and health-related correlates of physical activity and sedentary behaviour in individuals recently diagnosed with breast cancer. METHODS: Data were collected from 1381 participants within 90 days of diagnosis in the Alberta Moving Beyond Breast Cancer (AMBER) Cohort Study. Physical activity and sedentary behaviour were measured with ActiGraph GT3X+® and activPALTM devices, respectively, for seven consecutive days. Correlates were collected via a self-reported questionnaire, medical record extraction, or measured by staff. RESULTS: Multivariable models were fitted for sedentary behaviour, light physical activity, and moderate-to-vigorous physical activity. Greater sedentary behaviour was associated with higher body fat percentage (BF%) (ß=0.044; p<0.001) and being single (ß=0.542; p<0.002). Lower light physical activity was associated with higher BF% (ß=-0.044; p<0.001), higher body mass index (ß=-0.039; p<0.001), greater disease barrier influence (ß=-0.006; p<0.001), a HER2-positive diagnosis (ß=-0.278; p=0.001), and being single (ß=-0.385; p= 0.001). Lower moderate-to-vigorous physical activity was associated with higher BF% (ß =-0.011; p=0.001), greater disease barrier influence (ß=-0.002; p<0.001), and being of Asian (ß=-0.189; p=0.002) or Indian/South American (ß=-0.189; p=0.002) descent. Greater moderate-to-vigorous physical activity was associated with having greater intentions (ß=0.049; p=0.033) and planning (ß=0.026; p=0.015) towards physical activity. CONCLUSION: Tailoring interventions to increase physical activity for individuals recently diagnosed with breast cancer may improve long-term outcomes across the breast cancer continuum.

Depression, happiness, and satisfaction with life in women newly diagnosed with breast cancer: Associations with device-measured physical activity and sedentary time.

BACKGROUND: Few studies have examined depression after a cancer diagnosis and before initiating adjuvant or neoadjuvant systemic treatments. In this study, we present baseline data on device-measured physical activity, sedentary behaviour, depression, happiness, and satisfaction with life in newly diagnosed breast cancer survivors. PURPOSE: To examine associations of accelerometer-assessed physical activity and sedentary time with depression symptoms and prevalence, happiness, and satisfaction with life. METHODS: Shortly after diagnosis, 1425 participants completed depression, happiness, and satisfaction with life measures and wore an ActiGraph® device on their hip to measure physical activity and the activPALTM inclinometer on their thigh for 7 days to measure sedentary time (sitting/lying) and steps (1384 completed both device measures). ActiGraph® data were analysed using a hybrid machine learning method (R Sojourn package, Soj3x), and activPALTM data using activPALTM algorithms (PAL Software version 8). We used linear and logistic regression to examine associations of physical activity and sedentary time with depression symptom severity (0-27) and depression prevalence, happiness (0-100), and satisfaction with life (0-35). For the logistic regression analysis, we compared participants with none-minimal depression (n = 895) to participants with some depression (that is, mild, moderate, moderately-severe, or severe depression [n = 530]). RESULTS: Participants reported a mean depression symptom severity score of 4.3 (SD = 4.1), a satisfaction with life score of 25.7 (SD = 7.2), and a happiness score of 70 (SD = 21.8). Higher moderate-to-vigorous physical activity (MVPA) was associated with reduced depression symptom severity scores (ß = -0.51, 95% CI: -0.87 to -0.14, p = 0.007). A 1 hour increase in MVPA was associated with a reduced odds of at least mild or worse depression by 24% (Odds Ratio [OR] = 0.76, 95% CI: 0.62-0.94, p = 0.012). Higher daily step counts were associated with lower depression symptom severity scores (ß = -0.16, 95% CI: -0.24 to -0.10, p < 0.001). Perceptions of happiness was associated with higher MVPA (ß = 2.17, 95% CI: 0.17-4.17, p = 0.033). Sedentary time was not associated with depression severity, but higher sedentary time was associated with lower perceptions of happiness (ß = -0.80, 95% CI: -1.48 to -0.11, p = 0.023). CONCLUSIONS: Higher physical activity was associated with fewer depression symptom severity scores and reduced odds of mild or worse depression in women newly diagnosed with breast cancer. Higher physical activity and daily step counts were also associated with stronger perceptions of happiness and satisfaction with life, respectively. Sedentary time was not associated with depression symptom severity or odds of having depression, but was associated with stronger perceptions of happiness.

Associations between health-related fitness and quality of life in newly diagnosed breast cancer patients.

PURPOSE: Newly diagnosed breast cancer patients face substantial stress and uncertainty that may undermine their quality of life (QoL). The purpose of the present study was to examine the associations between health-related fitness (HRF) and QoL in newly diagnosed breast cancer patients from the Alberta Moving Beyond Breast Cancer Study. METHODS: Newly diagnosed breast cancer patients with early-stage disease (n = 1458) were recruited between 2012 and 2019 in Edmonton and Calgary, Canada to complete baseline HRF and QoL assessments within 90 days of diagnosis. HRF assessments included cardiorespiratory fitness (VO2peak treadmill test), muscular fitness (upper and lower body strength and endurance tests), and body composition (dual x-ray absorptiometry). QoL was assessed by the Medical Outcomes Study Short Form 36 (SF-36) version 2. We used logistic regression analyses to examine the associations between quartiles of HRF and poor/fair QoL (bottom 20%) after adjusting for key covariates. RESULTS: In multivariable analysis, the least fit groups compared to the most fit groups for relative upper body strength (OR = 3.19; 95% CI = 1.98-5.14), lean mass percentage (OR = 2.31; 95% CI = 1.37-3.89), and relative VO2peak (OR = 2.08; 95% CI = 1.21-3.57) were independently at a significantly higher risk of poor/fair physical QoL. No meaningful associations were found for mental QoL. CONCLUSIONS: The three main components of HRF (muscular fitness, cardiorespiratory fitness, and body composition) were independently associated with physical QoL in newly diagnosed breast cancer patients. Exercise interventions designed to improve these components of HRF may optimize physical QoL and help newly diagnosed breast cancer patients better prepare for treatments and recovery.

Prospective Cohort of Pre- and Post-Diagnosis Diet with Survival Outcomes: an Alberta Endometrial Cancer Cohort Study.

BACKGROUND: The prognostic relationship between diet and endometrial cancer survival remains largely unknown. We sought to determine pre- and post-diagnosis dietary composition, glycemic load (GL), inflammatory potential (dietary inflammatory index) and quality [Canadian Healthy Eating Index (C-HEI) 2005] associations with disease-free (DFS) and overall survival (OS) among endometrial cancer survivors. In addition, we assessed associations between dietary changes with OS and explored obesity/physical activity effect modification. METHODS: Survivors, diagnosed in Alberta, Canada between 2002 and 2006, completed past-year, food-frequency questionnaires at-diagnosis (n = 503) and 3-year follow-up (n = 395). Participants were followed to death or January 2022. Cox proportional regression estimated HR [95% confidence intervals (CI)] for dietary survival associations. RESULTS: During 16.9 median years of follow-up, 138 participants had a DFS event and 120 died. Lower pre-diagnosis GL (HRT1vsT3, 0.49; 95% CI, 0.25-0.97) and greater post-diagnosis energy intakes (EI) from total- and monounsaturated-fat (HRT3vsT1, 0.48; 95% CI, 0.26-0.87) were associated with better OS. Higher pre-diagnosis C-HEI, less inflammatory diets and lower added sugar intakes were nonlinearly associated with better DFS. Consistently low pre- to post-diagnosis EI from carbohydrates and total-fats were associated with better (HR, 0.36; 95% CI, 0.18-0.72) and worse (HR, 2.26; 95% CI, 1.21-4.20) OS, respectively. Decreased pre- to post-diagnosis C-HEI was associated with worse OS. In stratified analysis, healthy diets were most beneficial for survivors with obesity and physical inactivity. CONCLUSIONS: Adherence to higher quality dietary patterns were associated with better survival. IMPACT: Our study provides novel evidence that both pre- and post-diagnosis diet are important prognostic factors for endometrial cancer survivors. Post-diagnosis survival associations with diet composition and quality highlight the potential for future interventions.

Associations of device-measured physical activity and sedentary time with quality of life and fatigue in newly diagnosed breast cancer patients: Baseline results from the AMBER cohort study.

BACKGROUND: This study examined associations of device-measured physical activity and sedentary time with quality of life (QOL) and fatigue in newly diagnosed breast cancer patients in the Alberta Moving Beyond Breast Cancer (AMBER) cohort study. METHODS: After diagnosis, 1409 participants completed the SF-36 version 2 and the Fatigue Scale, wore an ActiGraph device on their right hip to measure physical activity, and an activPAL device on their thigh to measure sedentary time (sitting/lying) and steps. ActiGraph data was analyzed using a hybrid machine learning method (R Sojourn package, Soj3x) and activPAL data were analyzed using activPAL algorithms (PAL Software version 8). Quantile regression was used to examine cross-sectional associations of QOL and fatigue with steps, physical activity, and sedentary hours at the 25th, 50th, and 75th percentiles of the QOL and fatigue distributions. RESULTS: Total daily moderate and vigorous physical activity (MVPA) hours was positively associated with better physical QOL at the 25th (ß = 2.14, p = <.001), 50th (ß = 1.98, p = <.001), and 75th percentiles (ß = 1.25, p = .003); better mental QOL at the 25th (ß = 1.73, p = .05) and 50th percentiles (ß = 1.07, p = .03); and less fatigue at the 25th (ß = 4.44, p < .001), 50th (ß = 3.08, p = <.001), and 75th percentiles (ß = 1.51, p = <.001). Similar patterns of associations were observed for daily steps. Total sedentary hours was associated with worse fatigue at the 25th (ß = -0.58, p = .05), 50th (ß = -0.39, p = .06), and 75th percentiles (ß = -0.24, p = .02). Sedentary hours were not associated with physical or mental QOL. CONCLUSIONS: MVPA and steps were associated with better physical and mental QOL and less fatigue in newly diagnosed breast cancer patients. Higher sedentary time was associated with greater fatigue symptoms.

Energy balance in cancer survivors at risk of weight gain: a review.

PURPOSE: The study of energy balance [i.e., energy intake (EI) and energy expenditure (EE)] is a powerful tool for understanding body weight regulation and may contribute to our understanding of rapid weight gain risk in certain cancer survivors post-diagnosis. The purpose of this review was to summarize studies that assessed longitudinal, prospective changes in components of energy balance from diagnosis/start of treatment to any duration of follow-up in cancer survivors with prior evidence of weight gain (breast, prostate, thyroid, gynecologic, testicular, and acute lymphoblastic leukemia) RESULTS: The available literature suggests that energy balance components may be altered in cancer survivors who have a heightened risk of weight gain post-diagnosis. The evidence for EI was overall inconsistent. Conversely, decreases in resting and physical activity EE during the active phases of treatment (e.g., chemotherapy, hypothyroid state) were commonly noted, which then slowly rebounded towards baseline levels at the end of treatment and during follow-up assessments. Much of this evidence is based on data collected from breast cancer survivors, which highlights a paucity of data currently available on other cancer types. CONCLUSIONS: While there is growing acknowledgement that weight management interventions in cancer survivors are needed, it is important to recognize that changes in both behavioral (EI, physical activity EE) and passive (resting EE, thermic effect of food) components of energy balance may occur post-diagnosis. This information can help to inform weight management interventions which often entail modifications in diet and/or physical activity.

Associations of insulin resistance and inflammatory biomarkers with endometrial cancer survival: The Alberta endometrial cancer cohort study.

BACKGROUND: Metabolic dysfunction and inflammation have been associated with endometrial cancer risk; however, their influence on endometrial cancer survival is less understood. METHODS: A prospective cohort study of 540 endometrial cancer cases diagnosed between 2002 and 2006 in Alberta were followed for survival outcomes to 2019. Baseline blood samples collected either pre- or post-hysterectomy were analyzed for glucose, insulin, adiponectin, leptin, tumor necrosis factor-α, interleukin-6, and C-reactive protein. Covariates were obtained during in-person interviews and via medical chart abstraction. Cox proportional hazard regression models were used to estimate multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) for the association between each biomarker and disease-free and overall survival. RESULTS: Blood samples were collected from 520 of the 540 participants (presurgical n = 235; postsurgical n = 285). During the median follow-up of 14.3 years (range 0.4-16.5 years), there were 125 recurrences, progressions, and/or deaths with 106 overall deaths. None of the biomarkers were associated with disease-free or overall survival in multivariable-adjusted analyses. In an exploratory stratified analysis, the highest level of presurgical adiponectin, compared to the lowest level, was associated with improved disease-free (HR = 0.42, 95% CI = 0.20-0.85) and overall (HR = 0.41, 95% CI = 0.18-0.92) survival, whereas no statistically significant associations were noted for postsurgical measures of adiponectin. CONCLUSIONS: Overall, there was no evidence of an association between biomarkers of insulin resistance and inflammation with mortality outcomes in endometrial cancer survivors. Future cohort studies with serial blood samples are needed to understand the impact of changes in insulin resistance and inflammatory markers on endometrial cancer survival.

The Alberta moving beyond breast cancer (AMBER) cohort study: baseline description of the full cohort.

PURPOSE: The Alberta Moving Beyond Breast Cancer (AMBER) Study is an ongoing prospective cohort study investigating how direct measures of physical activity (PA), sedentary behavior (SB), and health-related fitness (HRF) are associated with survival after breast cancer. METHODS: Women in Alberta with newly diagnosed stage I (≥ T1c) to IIIc breast cancer were recruited between 2012 and 2019. Baseline assessments were completed within 90 days of surgery. Measurements included accelerometers to measure PA and SB; a graded treadmill test with gas exchange analysis to measure cardiorespiratory fitness (VO2peak); upper and lower body muscular strength and endurance; dual-X-ray absorptiometry to measure body composition; and questionnaires to measure self-reported PA and SB. RESULTS: At baseline, the 1528 participants' mean age was 56 ± 11 years, 59% were post-menopausal, 62% had overweight/obesity, and 55% were diagnosed with stage II or III disease. Based on device measurements, study participants spent 8.9 ± 1.7 h/day sedentary, 4.4 ± 1.2 h/day in light-intensity activity, 0.9 ± 0.5 h/day in moderate-intensity activity, and 0.2 ± 0.2 h/day in vigorous-intensity activity. For those participants who reached VO2peak, the average aerobic fitness level was 26.6 ± 6 ml/kg/min. Average body fat was 43 ± 7.1%. CONCLUSION: We have established a unique cohort of breast cancer survivors with a wealth of data on PA, SB, and HRF obtained through both direct and self-reported measurements. Study participants are being followed for at least ten years to assess all outcomes after breast cancer. These data will inform clinical and public health guidelines on PA, SB, and HRF for improving breast cancer outcomes.

Prospective Cohort Study of Pre- and Postdiagnosis Obesity and Endometrial Cancer Survival.

BACKGROUND: Disease-free survival (DFS) and overall survival (OS) associations with anthropometric measures of obesity and changes in these exposures remain unknown among endometrial cancer survivors. METHODS: Endometrial cancer survivors diagnosed between 2002 and 2006 completed direct anthropometric measurements and self-reported lifetime weight history during in-person interviews approximately 4 months after diagnosis (peridiagnosis) and approximately 3 years after diagnosis (follow-up). Participants were followed-up until death or March 20, 2019. Cox proportional regression was used to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for body mass index (BMI), weight, waist circumference, and waist-hip ratio with DFS and OS. Statistical tests were 2-sided. RESULTS: A total of 540 and 425 cancer survivors were assessed peridiagnosis and follow-up, respectively. During the median 14.2 years of follow-up (range = 0.3-16.5 years), 132 participants had a recurrence and/or died (DFS), with 111 deaths overall (OS). Reduced DFS was noted with greater recalled weight 1 year before diagnosis (HR = 1.88, 95% CI = 1.15 to 3.07), BMI 1 year before diagnosis (HR = 1.88, 95% CI = 1.09 to 3.22), and measured peridiagnosis BMI (HR = 2.04, 95% CI = 1.18 to 3.53). Measured peridiagnosis waist circumference of at least 88 cm was associated with decreased DFS (HR = 1.94, 95% CI = 1.24 to 3.03) and OS (HR = 1.90, 95% CI = 1.16 to 3.13). A twofold decrease in DFS and OS was associated with a BMI of at least 5% or weight change from 1 year before diagnosis to peridiagnosis. No associations were observed for the assessment during follow-up. CONCLUSIONS: One-year before- and peridiagnosis anthropometric measures of obesity were associated with reduced survival among endometrial cancer survivors. Anthropometric changes from 1 year before to peridiagnosis may provide an important indication of future survival in this population.

Dietary patterns with combined and site-specific cancer incidence in Alberta's Tomorrow Project cohort.

BACKGROUND/OBJECTIVES: Poor diet quality has been associated with an increased risk of cancer. Here, we examine the association between dietary patterns derived with two methods, and combined and site-specific cancer incidence in Canada. SUBJECTS/METHODS: Dietary data were obtained from participants enrolled in Alberta's Tomorrow Project, a prospective cohort study, between 2000 and 2008. Principle component analysis (PCA) and reduced rank regression (RRR) were used to derive dietary patterns, and data linkage with the Alberta Cancer Registry was used for incident cancer cases. Cox proportional hazard regressions were used to estimate multivariable-adjusted models for the association between each dietary pattern score with combined and site-specific cancer incidence. RESULTS: PCA revealed three dietary patterns ("western", "prudent", and "sugar, fruits, and dairy") and RRR resulted in four patterns ("dietary fiber", "vitamin D", "fructose", and "discretionary fat"). Five cancer sites were included in our site-specific analysis: lung, colon, breast, prostate, and endometrial cancers. The most protective dietary patterns for combined cancer sites were the "Prudent" pattern (HR = 0.82, CI = 0.73-0.92) and the "Dietary fiber" pattern (HR = 0.82, CI = 0.69-0.97). The "Fructose" pattern was associated with increased risk of combined cancers (HR = 1.14, CI = 1.02-1.27). Three dietary patterns were protective against colon cancer ("Prudent", "Dietary fiber", and "Discretionary fats"), and other risk reductions were seen for the "sugar, fruit, and dairy" pattern (lung cancer), and the "Dietary fiber" pattern (prostate cancer). CONCLUSIONS: These results support cancer prevention strategies for a diet high in vegetables, fruits, fish, and whole grains. Further studies should explore the possible association between discretionary fats and colon cancer.

Adherence to a lower versus higher intensity physical activity intervention in the Breast Cancer & Physical Activity Level (BC-PAL) Trial.

PURPOSE: The first aim is to examine adherence to a lower versus higher intensity physical activity (PA) prescription in breast cancer survivors in the Breast Cancer & Physical Activity Level (BC-PAL) Trial. The second aim is to assess associations between baseline characteristics with mean PA adherence in both intervention groups combined. METHODS: Forty-five participants were randomized to a 12-week, home-based lower (300 min/week, 40-59% heart rate reserve (HRR)) or higher (150 min/week, 60-80% HRR) intensity PA intervention, or no intervention/control. Both intervention groups received Polar A360® trackers and were included in this analysis (n=30). Study outcomes assessed on a weekly basis with the Polar A360® activity tracker throughout the intervention included relative adherence to the prescribed PA interventions (% of PA prescription goal met), and the absolute amount of PA time ≥40% of HRR. Baseline predictors of adherence included demographic characteristics, cardiorespiratory fitness, habitual PA and sedentary time, quality of life measures, and motivational variables from the Theory of Planned Behavior. For our primary aim, a linear mixed model was used to assess the effects of randomization group, time (intervention weeks 1-12), and the interaction of these factors on the natural logarithm of PA adherence. For our secondary aim, the association between each baseline predictor with the natural logarithm of mean weekly PA adherence was assessed, with randomization group added as a covariate. RESULTS: Higher relative time within the prescribed HRR zone was noted in the lower versus higher intensity PA groups (eß=3.12, 95% CI=1.97, 4.95). No differences in adherence across time were noted. Social support was inversely associated with relative PA time within the prescribed HRR zone (eß=0.83, 95% CI=0.72, 0.97) and absolute PA time ≥40% of HRR (eß= 0.82, 95% CI: 0.71, 0.93). Baseline VO2max was inversely associated with relative PA adherence (eß=0.98, 95% CI=0.95, 0.99). No other baseline measures were associated with PA adherence. CONCLUSIONS: There were no significant changes in absolute PA time ≥40% of HRR across time or between groups. However, the lower intensity PA group averaged over 3 times the relative amount of PA within the prescribed HRR zone compared to the higher intensity PA group. Finally, lower peer support and cardiorespiratory fitness at baseline were associated with higher PA adherence. IMPLICATIONS FOR CANCER SURVIVORS: The recent rise in popularity of commercially available activity trackers provides new opportunities to promote PA participation remotely, and these devices can be used to continuously and objectively measure PA levels as an indicator of intervention adherence. Future studies are needed to explore baseline predictors, facilitators, and barriers to sustained activity tracker use to promote PA behavior change and intervention adherence in cancer survivors. TRIAL REGISTRATION: This study was registered at www. CLINICALTRIALS: gov (No. NCT03564899) on June 21, 2018.

Dose-response effects of aerobic exercise on adiposity markers in postmenopausal women: pooled analyses from two randomized controlled trials.

BACKGROUND/OBJECTIVE: Exercise may reduce the risk of breast cancer through adiposity changes, but the dose-response effects of exercise volume on adiposity markers are unknown in postmenopausal women. We aimed to compare the dose-response effects of prescribed aerobic exercise volume on adiposity outcomes. PARTICIPANTS/METHODS: Data from the Alberta Physical Activity and Breast Cancer Prevention (ALPHA) and Breast Cancer and Exercise Trial in Alberta (BETA) were pooled for this analysis (N = 720). These were 12-month randomized controlled trials, where participants were randomized to 225 min/week (mid-volume) of aerobic exercise versus usual inactive lifestyle (ALPHA), or 150 min/week (low-volume) versus 300 min/week (high-volume) (BETA). Fat mass and fat-free mass were measured using DXA and intra-abdominal and subcutaneous fat area were assessed with computed tomography. RESULTS: After 12 months of aerobic exercise, increasing exercise volumes from no exercise/control to 300 min/week resulted in statistically significant reductions in BMI, weight, fat mass, fat percentage, intra-abdominal and subcutaneous fat area (P < 0.001). Compared with controls, fat mass loss was -1.13, -1.98 and -2.09 kg in the low-, mid- and high-volume groups, respectively. Similarly, weight loss was -1.47, -1.83, -2.21 kg in the low-, mid- and high-volume groups, respectively, compared to controls, and intra-abdominal fat area loss was -7.44, -15.56 and -8.76 cm2 in the low-, mid- and high-volume groups, respectively, compared to controls. No evidence for a dose-response effect on fat-free mass was noted. CONCLUSION: A dose-response effect of exercise volume on adiposity markers was noted, however, the differences in adiposity markers were smaller when comparing 225 min/week to 300 min/week of exercise. Given the strong positive associations between obesity and postmenopausal breast cancer risk, this study provides evidence on the importance of exercise volume as part of the exercise prescription to reduce adiposity and, ultimately, postmenopausal breast cancer risk.

Weight Regain and Breast Cancer-Related Biomarkers Following an Exercise Intervention in Postmenopausal Women.

BACKGROUND: Epidemiologic studies have reported associations between weight fluctuations and postmenopausal breast cancer risk; however, the biological markers involved in this association are unknown. This study aimed to explore the associations between breast cancer-related biomarkers and weight regain following exercise-induced weight loss. METHODS: From the 400 participants included in the Breast Cancer and Exercise Trial in Alberta, a total of 214 lost weight during the intervention and had follow-up blood samples, body composition, and covariate measurements. Outcomes were measured at baseline, 12 months (end of the study), and 24 months (follow-up). RESULTS: During follow-up, weight regain was 1.80 kg [95% confidence interval (CI): -0.40-3.90], and was significantly associated with increases in estradiol [treatment effect ratio (TER) = 1.03; 95% CI, 1.01-1.04], estrone (TER = 1.02; 95% CI, 1.01-1.03), free estradiol (TER = 1.04; 95% CI, 1.02-1.05), the homeostatic model assessment for insulin resistance (TER = 1.03; 95% CI, 1.02-1.05), and insulin (TER = 1.03; 95% CI, 1.01-1.04), and decreases in sex hormone-binding globulin (SHBG; TER = 0.98; 95% CI, 0.97-0.99) levels. Nonstatistically significant associations were found for glucose and C-reactive protein. Furthermore, a statistically significant linear trend of increasing levels for all biomarkers, and decreasing SHBG, across weight regain categories was found. CONCLUSIONS: These results suggest that weight regain following exercise-induced weight loss is associated with breast cancer-related biomarker changes in postmenopausal women. IMPACT: These findings provide evidence to support the importance of developing effective strategies to prevent weight regain and, consequently, decrease postmenopausal breast cancer risk via changes in adiposity-related biomarkers.

Physical activity, obesity and sedentary behavior in cancer etiology: epidemiologic evidence and biologic mechanisms.

An estimated 30-40% of cancers can be prevented through changes in modifiable lifestyle and environmental risk factors known to be associated with cancer incidence. Despite this knowledge, there remains limited awareness that these associations exist. The purpose of this review article was to summarize the epidemiologic evidence concerning the contribution of physical activity, sedentary behavior, and obesity to cancer etiology and to provide an overview of the biologic mechanisms that may be operative between these factors and cancer incidence. Strong and consistent evidence exists that higher levels of physical activity reduce the risk of six different cancer sites (bladder, breast, colon, endometrial, esophageal adenocarcinoma, gastric cardia), whereas moderate evidence inversely associates physical activity with lung, ovarian, pancreatic and renal cancer, and limited evidence inversely correlates physical activity with prostate cancer. Sedentary behavior, independent of physical activity, has been shown to increase the risk of colon, endometrial, and lung cancers. Obesity is an established risk factor for 13 different cancer sites (endometrial, postmenopausal breast, colorectal, esophageal, renal/kidneys, meningioma, pancreatic, gastric cardia, liver, multiple myeloma, ovarian, gallbladder, and thyroid). The main biologic mechanisms whereby physical activity, sedentary behavior, and obesity are related to cancer incidence include an effect on endogenous sex steroids and metabolic hormones, insulin sensitivity, and chronic inflammation. Several emerging pathways related to oxidative stress, DNA methylation, telomere length, immune function, and gut microbiome are presented. Key recommendations for future research in both the epidemiology and biology of the associations between physical activity, sedentary behavior, obesity, and cancer risk are also provided.

Social Jetlag and Prostate Cancer Incidence in Alberta's Tomorrow Project: A Prospective Cohort Study.

We investigated the association of social jetlag (misalignment between the internal clock and socially required timing of activities) and prostate cancer incidence in a prospective cohort in Alberta, Canada. Data were collected from 7455 cancer-free men aged 35-69 years enrolled in Alberta's Tomorrow Project (ATP) from 2001-2007. In the 2008 survey, participants reported usual bed- and wake-times on weekdays and weekend days. Social jetlag was defined as the absolute difference in waking time between weekday and weekend days, and was categorized into three groups: 0-<1 h (from 0 to anything smaller than 1), 1-<2 h (from 1 to anything smaller than 2), and 2+ h. ATP facilitated data linkage with the Alberta Cancer Registry in June 2018 to determine incident prostate cancer cases (n = 250). Hazard ratios (HR) were estimated using Cox proportional hazards regressions, adjusting for a range of covariates. Median follow-up was 9.57 years, yielding 68,499 person-years. Baseline presence of social jetlag of 1-<2 h (HR = 1.52, 95% CI: 1.10 to 2.01), and 2+ hours (HR = 1.69, 95% CI: 1.15 to 2.46) were associated with increased prostate cancer risk vs. those reporting no social jetlag (p for trend = 0.004). These associations remained after adjusting for sleep duration (p for trend = 0.006). With respect to chronotype, the association between social jetlag and prostate cancer risk remained significant in men with early chronotypes (p for trend = 0.003) but attenuated to null in men with intermediate (p for trend = 0.150) or late chronotype (p for trend = 0.381). Our findings suggest that greater than one hour of habitual social jetlag is associated with an increased risk of prostate cancer. Longitudinal studies with repeated measures of social jetlag and large samples with sufficient advanced prostate cancer cases are needed to confirm these findings.

Prospective Cohort Study of Pre- and Postdiagnosis Physical Activity and Endometrial Cancer Survival.

PURPOSE: The aim of this study was to evaluate associations between pre- and postdiagnosis physical activity and survival in survivors of endometrial cancer by physical activity domain, intensity, dose (metabolic-equivalent task [MET]-hours/week/year), and change from pre- to postdiagnosis. METHODS: We conducted a prospective cohort study in Alberta, Canada, of 425 women who were diagnosed with histologically confirmed invasive endometrial cancer between 2002 and 2006 and observed to 2019. The interviewer-administered Lifetime Total Physical Activity Questionnaire recorded prediagnosis (assessed at a median of 4.4 months after diagnosis) and postdiagnosis physical activity (assessed at a median of 3.4 years after diagnosis). Associations between physical activity and overall and disease-free survival were assessed using Cox proportional hazards models adjusted for age, stage, grade, treatments, body mass index, menopausal status, hormone therapy use, family history of cancer, and comorbidities. RESULTS: After a median follow-up of 14.5 years, there were 60 deaths, including 18 endometrial cancer deaths, and 80 disease-free survival events. Higher prediagnosis recreational physical activity was statistically significantly associated with improved disease-free survival (> 14 v ≤ 8 MET-hours/week/year; hazard ratio [HR], 0.54; 95% CI, 0.30 to 0.96; Ptrend = .04), but not overall survival (HR, 0.56; 95% CI, 0.29 to 1.07; Ptrend = .06). Higher postdiagnosis recreational physical activity (> 13 v ≤ 5 MET-hours/week/year) was strongly associated with both improved disease-free survival (HR, 0.33; 95% CI, 0.17 to 0.64; Ptrend = .001) and overall survival (HR, 0.33; 95% CI, 0.15 to 0.75; Ptrend = .007). Participants who maintained high recreational physical activity levels from pre- to postdiagnosis also had improved disease-free survival (HR, 0.35; 95% CI, 0.18 to 0.69) and overall survival (HR, 0.43; 95% CI, 0.20 to 0.94) compared with those who maintained low physical activity levels. CONCLUSION: Recreational physical activity, especially postdiagnosis, is associated with improved survival in survivors of endometrial cancer.

Prospective cohort study of metabolic syndrome and endometrial cancer survival.

OBJECTIVE: Comorbidities are known to increase endometrial cancer risk, but the separate and combined impact of these risk factors on endometrial cancer survival remains unclear. This study aimed to determine the associations between metabolic syndrome and its components with disease-free survival, overall survival, endometrial cancer-specific survival and recurrence among endometrial cancer survivors. METHODS: Cases from a population-based case-control study who were diagnosed with primary endometrial cancer between 2002 and 2006 in Alberta, Canada were followed until death or March 20, 2019. Baseline in-person interviews, direct anthropometric measurements and fasting blood samples were used to assess metabolic syndrome (presence of ≥3 of the following: waist circumference ≥ 88 cm, fasting blood glucose ≥100 mg/dL, triglycerides ≥150 mg/dL, high-density lipoprotein cholesterol <50 mg/dL and self-reported hypertension). Cox proportional hazards regression and Fine and Gray competing risk models were used to estimate multivariate-adjusted hazard ratios (95% CI) for these associations. RESULTS: Among 540 endometrial cancer survivors, 325 had metabolic syndrome at diagnosis and 132 had a recurrence and/or died during the median 14.2 years of follow-up (range: 0.3-16.5 years). In multivariable analyses, being diagnosed with metabolic syndrome (HR = 1.98, 95% CI = 1.07-3.67) and having an elevated waist circumference (≥88 cm; HR = 2.12, 95% CI = 1.18-3.80; HRper 5 cm = 1.21, 95% CI = 1.07-1.36) were associated with worse overall survival. Additionally, increasing waist circumference (per 5 cm) was also associated worse with disease-free survival (HRper 5 cm = 1.11, 95% CI = 1.00-1.24). CONCLUSION: The metabolic syndrome, in particular central adiposity, were associated with worse overall and disease-free survival in endometrial cancer survivors.