Risk Factors for Second Primary Cancer in a Prospective Cohort of Endometrial Cancer Survivors: an Alberta Endometrial Cancer Cohort Study.

We examined associations between modifiable and non-modifiable cancer-related risk factors measured at endometrial cancer diagnosis and during early survivorship (~3 years post-diagnosis) with second primary cancer (SPC) risk among 533 endometrial cancer survivors in the Alberta Endometrial Cancer Cohort using Fine and Gray sub-distribution hazard models. During a median follow-up of 16.7 years (interquartile range (IQR)=12.2-17.9), 89 (17%) participants developed a SPC with breast (29%), colorectal (13%) and lung (12%) cancers being the most common. Dietary glycemic load before endometrial cancer diagnosis (≥90.4 vs. <90.4 g/day: sub-hazard ratios (sHR)=1.71, 95% confidence intervals (CI)=1.09-2.69) as well as older age (≥60 vs. <60: sHR=2.48, 95% CI=1.34-4.62) and alcohol intake (≥2 drink/week vs. none: sHR=3.81, 95% CI=1.55-9.31) during early survivorship were associated with increased SPC risk. Additionally, reductions in alcohol consumption from prediagnosis to early survivorship significantly reduced SPC risk (sHR=0.34, 95% CI=0.14-0.82). With one-in-six survivors developing a SPC, further investigation of SPC risk factors and targeted surveillance options for high-risk survivors could improve long-term health outcomes in this population. Reductions in dietary glycemic load and alcohol intake from prediagnosis to early survivorship showed promising risk reductions for SPCs and could be important modifiable risk factors to target among endometrial cancer survivors.

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.

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 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.

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.

Obesity and mortality among endometrial cancer survivors: A systematic review and meta-analysis.

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.

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.

Breast cancer survivors' perspectives on a home-based physical activity intervention utilizing wearable technology.

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 acrchversusfear 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.