Purpose: To gain breast cancer survivors' perspectives on participation in a home-based physical activity intervention and the factors that contributed to their acceptance and adherence to physical activity. Methods: Semi-structured interviews were conducted with six women who had participated in a 12-week, home-based physical activity intervention using Polar A360® activity trackers. Additionally, 22 participants from the physical activity interventions provided scaled responses to barriers of physical activity on weeks 3, 6, 9, and 12. Interviews were transcribed verbatim. Thematic analysis was used for qualitative data. Results: Perceptions (n = 6) were categorized into three main themes including (i) Study Environment which consisted of three subthemes acrch versus fear of failure, power of results, and reminders of cancer and moving beyond. (ii) Influence of People encompassed two subthemes, i.e., personal relationships and self as a source of motivation; and (iii) Wearable Technology which was divided into two subthemes, i.e., objective insights into health and disconnect of person and technology. From the scaled responses, the most impactful barriers for participants within the intervention groups (n = 22) were "feeling busy," "lack of motivation," and "weather." Conclusion: Wearable technology was perceived largely as a facilitator to physical activity in the current study, but technologic difficulties created a barrier to physical activity adherence. Additionally, participants' perceptions of study design elements and social support influenced their acceptance and adherence to the home-based physical activity interventions and should be considered to inform the design and implementation of future studies.

Background: Metabolic syndrome has been previously associated with increased endometrial cancer risk, but the relationship with metabolic syndrome and endometrial cancer survival remains unclear. Objectives: To determine the associations between metabolic syndrome using the harmonized criteria with disease-free survival, overall survival, endometrial cancer-specific survival and time to recurrence among endometrial cancer survivors. Second, to determine the association between the number of metabolic syndrome components as well as each individual metabolic syndrome component with these prognostic outcomes. Methods: A prospective cohort of 540 endometrial cancer survivors diagnosed between 2002 and 2006 participated in the Alberta Endometrial Cancer Cohort and 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. Recurrence and survival data were obtained via medical chart abstraction and vital status updates. Results: Compared to endometrial cancer survivors without metabolic syndrome, survivors with metabolic syndrome had worse overall survival when assessed with the harmonized criteria. Of the individual metabolic syndrome components, only waist circumference was associated with recurrence and survival outcomes. Lifetime recreational physical activity prior to diagnosis was observed to modify the associations between metabolic syndrome and its components with overall survival and disease-free survival. Conclusion: The metabolic syndrome, especially waist circumference, was associated with worse overall and disease-free survival among endometrial cancer survivors. Future research should aim to confirm these results and improve our understanding of the role lifestyle factors iii such as physical activity have in the association between metabolic syndrome and endometrial cancer survivors' prognosis. iv Preface Chapter Four includes the main manuscript from this thesis which addresses the association between metabolic syndrome and its components defined by harmonized criteria with disease-free survival, overall survival, endometrial cancer-specific survival and recurrence among endometrial cancer survivors from the Alberta Endometrial Cancer Cohort Study. For this manuscript Renee Kokts-Porietis led the formal analysis and interpretation of data, as well as drafting, writing, reviewing and editing of the manuscript. All authors were involved in conceptualization and provided critical review of this manuscript. Kerry Courneya, Linda Cook and Christine Friedenreich were involved in the funding acquisition, methodology, investigation and project administration of the larger project. Finally, Jessica McNeil, Gregg Nelson and Christine Friedenreich provided supervision and guidance to Renee Kokts-Porietis at each stage of the project.

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.

Summary Excess body fat is a major risk factor for endometrial cancer incidence, but its impact on recurrence and survival remains unclear. The aim of this systematic review and meta‐analysis was to assess the association between excess body fat with recurrence, cancer‐specific, and all‐cause mortality among endometrial cancer survivors. We searched MEDLINE and EMBASE databases up to July 2021. Risk of bias was assessed with the Ottawa Newcastle Scale. Random effects models estimated pooled hazard ratios for the main associations between body mass index (BMI) and survival outcomes and stratified by endometrial cancer type. Potential heterogeneity and publication bias were evaluated with sensitivity analyses, funnel plots, and Egger's test. Forty‐six studies were included, of which 45 estimated body fat with BMI and six used direct waist circumference measures or CT/MRI scans. Higher BMI (≥30 kg/m2) was associated with increased all‐cause mortality (HR = 1.34, 95%CI = 1.12–1.59) and recurrence (HR = 1.28, 95%CI = 1.06–1.56). In sub‐group analysis, associations between higher BMI and all‐cause mortality were observed for both Types I and II survivors, while recurrence associations were only significant among Type I cases. Obesity at endometrial cancer diagnosis was associated with increased cancer recurrence and all‐cause mortality among endometrial cancer survivors but not endometrial cancer‐specific mortality.

Background Disease-free and overall survival associations with anthropometric measures of obesity and changes in these exposures remain unknown among endometrial cancer survivors. Methods Endometrial cancer survivors diagnosed between 2002–2006 completed direct anthropometric measurements and self-reported lifetime weight history during in-person interviews approximately 4 months after diagnosis (peri-diagnosis) and approximately 3 years after diagnosis (follow-up). Participants were followed until death or March 20, 2019. Cox proportional regression estimated multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) for body mass index (BMI), weight, waist circumference, and waist-hip ratio with disease-free survival (DFS) and overall survival (OS). Statistical tests were two-sided. Results 540 and 425 cancer survivors were assessed peri-diagnosis 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 one-year before-diagnosis (HR = 1.88, 95% CI = 1.15 to 3.07), BMI one-year before-diagnosis (HR = 1.88, 95% CI = 1.09 to 3.22), and measured peri-diagnosis BMI (HR = 2.04, 95% CI = 1.18 to 3.53). Measured peri-diagnosis waist circumference ≥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 two-fold decrease in DFS and OS was associated with ≥5% BMI or weight change from one-year before diagnosis to peri-diagnosis. No associations were observed for the assessment during follow-up. Conclusion One-year before- and peri-diagnosis anthropometric measures of obesity were associated with reduced survival among endometrial cancer survivors. Anthropometric changes from one-year before- to peri-diagnosis may provide an important indication of future survival in this population.

Abstract. Heart rate variability (HRV) is a biomarker used to reflect both healthy and pathological state(s). The effect of the menstrual cycle and menstrual cycle phases (follicular, luteal) on HRV remains unclear. Active eumenorrheic women free from exogenous hormones completed five consecutive weeks of daily, oral basal body temperature (BBT) and HRV measurements upon waking. Descriptive statistics were used to characterize shifts in the HRV measures: standard deviation of NN intervals (SDNN), root mean square of successive difference (rMSSD), high (HF) and low frequency (LF) across the menstrual cycle and between phases. All HRV measures were assessed by medians ( Mdn), median difference of consecutive days ( Mdn∆) and variance. Seven participants ( M ±  SD; age: 28.60 ± 8.40 year) completed the study with regular menstrual cycles (28.40 ± 2.30 days; ovulation day 14.57 ± 0.98 day). Median rMSSD displayed a nonlinear decrease across the menstrual cycle and plateau around the day of ovulation. A negative shift before ovulation in Mdn∆, rMSSD, SDNN, and LF as well as peak on luteal phase Day 4 in rMSSD and SDNN was observed. Median variance increased in rMSSD (150.06 ms2) SDNN (271.12 ms2), and LF variance (0.001 sec2/Hz) from follicular to luteal phase. Daily HRV associated with the parasympathetic nervous system was observed to decrease nonlinearly across the menstrual cycle.

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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 (DII)) and quality (Canadian-Health Eating Index (C-HEI) 2005) associations with disease-free (DFS) and overall survival (OS) among endometrial cancer survivors. Additionally, we assessed associations between dietary changes with OS and explored obesity/physical activity effect modification. Methods: Survivors, diagnosed in Alberta, Canada between 2002-2006, completed past-year, food-frequency questionnaires at-diagnosis (n=503) and three-year follow-up (n=395). Participants were followed to death or January 2022. Cox proportional regression estimated HR (95% confidence intervals (CIs)) 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 non-linearly 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. Conclusion: 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.