Abstract Background Insufficient physical activity (PA) and excessive sedentary behaviour is associated with several cancers. Personalised approaches to increasing healthy movement behaviours over unhealthy behaviours may be more effective than a one-size-fits-all approach. Exploring both postures, and intensities across the 24-hour day may reveal actionable behavioural alternatives from current guidance. Methods Using a novel dual-compositional approach, we assessed how differences in participant’s composition of 24-hour daily movement (postures and intensities) and sleep are differentially associated with PA-related cancer incidence (a composite of 13 sites linked with physical inactivity). This prospective analysis involved adults drawn from the UK Biobank accelerometry subsample each followed-up by health linkage. Participant’s daily movement was classified into two 24-hour compositions. Composition 1 (posture-focused): sleep duration, sedentary behaviour (SB), standing, moving at any intensity. Composition 2 (intensity-focused): sleep duration, sedentary time (ST), light PA (LPA), moderate PA (MPA), and vigorous PA (VPA). Secondary analysis combined VPA and MPA as moderate-to-vigorous PA (MVPA). PA-related cancer diagnoses were captured from health registry data for up to 9.5 years (y). Cox-proportional hazards models were adjusted for age, sex, education, smoking, alcohol, diet, parental cancer history, cardiovascular disease and medication use. Results Analyses included 59,218 (55% female) participants (mean [SD] age: 61.7 [7.8]y), with a median follow-up of 8.0y [IQR: 7.4-8.5y; 464,640 person years] with 2,385 (4%) incident cancer events. Among the average, active participant, greater moving in place of other behaviours was associated with lower cancer risk, e.g. theoretically replacing 15 min of sleep or SB with 15 min of moving was associated with hazard ratios (HR) of 0.98 (95% Confidence Interval (95%CI): 0.97–0.99) and 0.98 (95%CI: 0.97–0.99), respectively. Similar risk reduction was observed with 30 min additional standing in place of sleep or SB. Regarding intensity, greater MVPA, in place of any behaviour proved most robustly associated with lower risk, although notably, the VPA component within MVPA proved the critical intensity. Conclusions Beyond MVPA, moving at any intensity, in place of other postures, was associated with reduced risk of cancer. However, greater standing may also provide a plausible behavioural adjunct or alternative, warranting further investigation.

Purpose To examine the associations between pre-diagnosis exogenous hormone exposure and endogenous sex hormone levels shortly after diagnosis with survival outcomes in endometrial cancer survivors. Methods In this population-based cohort, females with endometrial cancer were followed from diagnosis to death or January 27, 2022. History of hormone exposure pre-diagnosis and sex-hormone levels shortly after diagnosis were obtained. The associations between hormone exposure and sex-hormone levels with disease-free survival (DFS) and overall survival (OS) were estimated using Cox proportional hazards regression by multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Results During a median 16.9 years of follow-up (IQR = 15.5–18.1 years), 152 of the 540 participants had a recurrence and/or died. There were no statistically significant associations between exposure to hormonal contraception or menopausal hormone therapy before diagnosis and DFS or OS. Higher estrone levels post-diagnosis were associated with lower DFS (HR 1.56, 95% CI 1.04–2.34) and lower OS (HR 1.76, 95% CI 1.15–2.72). Lower DFS was also observed with higher estradiol levels (HR 1.56, 95% CI 1.02–2.41). Conclusion There were no associations between pre-diagnosis hormonal contraception or menopausal hormone therapy use and endometrial cancer survival in our study. Endometrial cancer survivors with higher estrogen levels shortly after diagnosis had lower DFS and OS. Further research is needed to confirm these findings.

Purpose Whether physical activity is associated with the risk of cancer among adults with a cardiometabolic disease is not well understood. This study investigated associations between physical activity and cancer risk in adults with and without a history of cardiometabolic diseases (cardiovascular disease and/or type 2 diabetes). Methods We conducted a meta-analysis of individual participant data of 564,622 men and women, aged 35–70 years at recruitment, across six European countries from the European Prospective Investigation into Cancer and Nutrition (EPIC) and UK Biobank. We excluded participants from these cohorts who had cancer, cardiovascular disease, or type 2 diabetes at baseline. Data on physical activity were assessed at baseline with self-reported validated questionnaires and modelled as metabolic equivalent task hours per week (MET-h/week). We used multivariable-adjusted Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between physical activity and the risk of physical activity-related cancers, with a multiplicative interaction between physical activity and time-varying cardiometabolic disease status. Results After a median of 11 years of follow-up, 28,345 participants developed a first primary physical activity-related cancer (EPIC and UK Biobank combined). In the meta-analysis of both cohorts, a 1 standard deviation (SD) increment of physical activity was associated with a lower risk of physical activity-related cancer, with HRs of 0.96 (95% CI: 0.95, 0.97) and 0.94 (95% CI: 0.90, 0.99) in adults without and in those with a cardiometabolic disease, respectively (p-interaction > 0.3). Conclusions The findings of this study among European adults suggest that higher physical activity is equally beneficial for cancer prevention in adults with and without underlying cardiometabolic diseases.

Objective:To assess whether procedural-induced abortion or provider-initiated preterm delivery are associated with improved survival in pregnant people with cancer. Design: Retrospective population-based cohort study. Setting: Provinces of Alberta and Ontario, Canada, 2003-2016. Population: Females aged 18-50 years diagnosed with cancer at <20 weeks' (for the assessment of procedural-induced abortion) or <37 weeks' gestation (for the assessment of provider-initiated delivery). Methods: Cox proportional hazard models assessed all-cause mortality in relation to procedural-induced abortion and provider-initiated preterm delivery, adjusting for cancer site, stage at diagnosis and age. Meta-analysis pooled the results across both provinces. Main Outcome MeasuresAll cause mortality. Results: There were 512 pregnant people diagnosed with cancer at <20 weeks' gestation and 782 diagnosed with cancer at <37 weeks' gestation. Neither procedural-induced abortion (adjusted hazard ratio [aHR] = 1.39, 95% CI: 0.32-6.17) nor provider-initiated preterm delivery (aHR = 1.17, 95% CI: 0.76-1.81) were associated with improved survival following adjustment for age, stage at diagnosis and cancer site. Conclusions: Neither procedural-induced abortion nor provider-initiated preterm birth was associated with improved survival in pregnant people diagnosed with cancer; however, these obstetric interventions are highly personal decisions best decided by the pregnant person in consultation with their care providers.

OBJECTIVE:Low body fat and high physical activity levels are key lifestyle factors in cancer prevention, but the interplay of abdominal obesity and physical activity on cancer risk remains unknown. We explored individual and joint associations of waist circumference and physical activity with cancer risk. METHODS:Using UK Biobank data (n=315 457), we categorised individuals according to WHO guideline thresholds for waist circumference and self-reported physical activity levels. Multivariable-adjusted Cox regression was used to estimate HRs and 95% CIs of total cancer. The reference group comprised individuals with recommended levels of waist circumference (<88 cm for women and <102 cm for men) and physical activity (>10 metabolic equivalent of task hours/week). Furthermore, we estimated the proportion of cancers attributable to abdominal obesity and insufficient physical activity. RESULTS:During a median follow-up period of 11 years (3 321 486 person-years), 29 710 participants developed any type of cancer. Participants not meeting the WHO guideline on waist circumference had increased cancer risk, even when sufficiently physically active according to the WHO (HR 1.11, 95% CI 1.08 to 1.15). Similarly, individuals not achieving the WHO guideline for physical activity showed an elevated risk, even if they were abdominally lean (HR 1.04, 95% CI 1.01 to 1.07). Not adhering to either guideline yielded the strongest increase in risk (HR 1.15, 95% CI 1.11 to 1.19). We estimated that abdominal obesity coupled with insufficient physical activity could account for 2.0% of UK Biobank cancer cases. CONCLUSION:Adherence to both WHO guidelines for waist circumference and physical activity is essential for cancer prevention; meeting just one of these guidelines is insufficient.

BACKGROUND:Preclinical and observational studies suggest that exercise may improve cancer outcomes. However, definitive level 1 evidence is lacking. METHODS:In this phase 3, randomized trial conducted at 55 centers, we assigned patients with resected colon cancer who had completed adjuvant chemotherapy to participate in a structured exercise program (exercise group) or to receive health-education materials alone (health-education group) over a 3-year period. The primary end point was disease-free survival. RESULTS:From 2009 through 2024, a total of 889 patients underwent randomization to the exercise group (445 patients) or the health-education group (444 patients). At a median follow-up of 7.9 years, disease-free survival was significantly longer in the exercise group than in the health-education group (hazard ratio for disease recurrence, new primary cancer, or death, 0.72; 95% confidence interval [CI], 0.55 to 0.94; P = 0.02). The 5-year disease-free survival was 80.3% in the exercise group and 73.9% in the health-education group (difference, 6.4 percentage points; 95% CI, 0.6 to 12.2). Results support longer overall survival in the exercise group than in the health-education group (hazard ratio for death, 0.63; 95% CI, 0.43 to 0.94). The 8-year overall survival was 90.3% in the exercise group and 83.2% in the health-education group (difference, 7.1 percentage points; 95% CI, 1.8 to 12.3). Musculoskeletal adverse events occurred more often in the exercise group than in the health-education group (in 18.5% vs. 11.5% of patients). CONCLUSIONS:A 3-year structured exercise program initiated soon after adjuvant chemotherapy for colon cancer resulted in significantly longer disease-free survival and findings consistent with longer overall survival. (Funded by the Canadian Cancer Society and others; CHALLENGE ClinicalTrials.gov number, NCT00819208.).

Background: Cancer, cardiovascular diseases (CVD), and type 2 diabetes (T2D) may co-occur, a condition referred to as multimorbidity. Physical activity is inversely associated with each of these diseases; however, the biologic pathways underlying these relationships remain incompletely understood. Methods: In 33,806 UK Biobank participants, we derived a proteomic signature (high-throughput panel of 2,911 proteins assessed by Olink array) of moderate-to-vigorous physical activity using linear and LASSO regressions in a two-step procedure to prospectively assess associations with physical activity-related cancers (1,108 cases), CVD (3,445 cases), T2D (1,363 cases), as well as progression to multimorbidity (420 cases). Multivariable Cox regression estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for each identified protein, as well as their linear combination (proteomics signature score), separately for each outcome and with adjustment for physical activity. Pathway enrichment analysis and protein-protein interaction networks were used to gain insights into the systemic interplay of the identified proteins. Results: After correction for multiple testing, 223 proteins were selected in the physical activity signature. Proteins involved in food intake, metabolism, and cell growth regulation (e.g., LEP, MSTN, TGFBR2) were inversely associated with physical activity. Proteins involved in immune cell adhesion and migration, as well as cartilage and muscle integrity (e.g., integrins, COMP, MYOM3) were positively associated with physical activity. Several proteins upregulated by physical activity were inversely associated with disease risk (e.g., integrins, PI3, CLEC4A for cancer risk, or LPL, IGFBP1, LEP for T2D risk). Similarly, various proteins were downregulated by physical activity and positively associated with disease risk (e.g., CD38, TGFA for CVD risk). For multimorbidity, proteins inversely related to physical activity generally aligned with expected risk patterns, while positively associated proteins exhibited mixed effects, with inverse and positive associations. The proteomics signature score was inversely associated with the risk of cancer (HR per interquartile range: 0.87; 95% CI: 0.78, 0.96) and T2D (HR: 0.66; 95% CI: 0.60, 0.72), after adjustment for physical activity, but not with CVD (HR: 0.93; 95% CI: 0.85, 1.03) and progression towards multimorbidity. Conclusions: These findings suggest that the inverse relationships between physical activity and risk of major chronic diseases may be explained by the maintenance of tissue integrity and the proper regulation of immune and metabolic processes. Further studies are needed to determine the causal nature of these associations. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Funding for IIG\_FULL\_2021\_027 was obtained from World Cancer Research Fund (WCRF UK), as part of the World Cancer Research Fund International grant programme. This study was supported by the French National Cancer Institute (l'Institut National du Cancer, INCA\_16824), the German Research Foundation (BA 5459/2-1). The UK Biobank was supported by the Wellcome Trust, Medical Research Council, Department of Health, Scottish government, and Northwest Regional Development Agency. It has also had funding from the Welsh Assembly government and British Heart Foundation. The research was designed, conducted, analysed, and interpreted by the authors entirely independently of these funding sources. The funder had no role in study design, data acquisition and analysis, decision to publish, or preparation of the manuscript. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical approval was obtained from the North West Multi-Centre Research Ethics Committee (21/NW/0157). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes UK Biobank is an open access resource. Bona fide researchers can apply to use the UK Biobank dataset by registering and applying at http://ukbiobank.ac.uk/register-apply/.

The effects of exercise on cancer outcomes may differ depending on its positioning within different cancer treatment combinations. We examined whether the associations between physical activity (PA) and cancer outcomes varied by cancer treatment modality or timing of PA. We conducted a secondary analysis of the Prostate Cancer Cohort Study consisting of 830 men in Alberta, Canada with newly diagnosed prostate cancer. Lifetime prediagnosis PA was assessed by an in-person interview shortly after diagnosis whereas postdiagnosis PA was assessed at 2–3 year intervals by an in-person interview (first follow-up) or self-report (second and third follow-ups). Cox proportional hazards regression models were used to test interactions between PA and treatment modalities for disease-free survival, overall survival, and prostate cancer-specific disease-free survival. Postdiagnosis vigorous PA significantly interacted with surgery (p < 0.001) and radiotherapy (p = 0.003). Specifically, patients who had surgery experienced a 61

BACKGROUND:Most studies investigating physical activity and cancer risk used a single-time measure of physical activity. The present analysis investigates whether changes in physical activity during midlife influence cancer risk. METHODS:A prospective cohort of adults ≥40 years from the UK Biobank who provided self-reported physical activity data via the International Physical Activity Questionnaire at both baseline (2007-2010) and follow-up (2012-2013) was analyzed. Changes in physical activity were classified as decreased, maintained, or increased between these two time points. Incident cancers were ascertained up to May 13, 2022. Multivariable Cox regressions were used to examine the associations between changes in physical activity and the risk of cancer overall, by sex, and by obesity- versus nonobesity-related cancers and for breast and prostate cancers. RESULTS:A total of 16,792 participants [mean (SD) age, 56.8 (7.4); 8,421 (50.2%) females] provided repeated data on physical activity. During a median follow-up of 8.3 years, 1,397 incident cancer cases occurred. No statistically significant associations between changes in physical activity and overall cancer risk were found. Increasing physical activity from low to higher levels was associated with a lowered risk of obesity-related cancer [HR = 0.72; 95% confidence interval (CI), 0.54-0.95], particularly for the risk of breast cancer (HR = 0.61; 95% CI, 0.36-1.04). Females who decreased their physical activity from high to lower levels had an elevated cancer risk (HR = 1.47; 95% CI, 1.02-2.11). CONCLUSIONS:Increasing physical activity over time was associated with a lower risk of developing obesity-related cancers, particularly breast cancer. IMPACT:Our findings suggest that behavioral changes to increase physical activity in midlife may help reduce cancer risk.

BACKGROUND:Few studies have prospectively examined how changes in physical activity in the first year after a breast cancer diagnosis may affect patient-reported outcomes (PROs) including quality of life and fatigue. PURPOSE:The purpose of this study was to examine changes in device-measured physical activity and associations with changes in quality of life [physical composite summary score (PCS) and mental composite summary score (MCS)] and fatigue from the first year after diagnosis among newly diagnosed women with breast cancer in the Alberta Moving Beyond Breast Cancer Study. METHODS:In this prospective cohort study, we assessed women within a median of 60 days postsurgery (N = 1442) and again 1 year later (N = 1194). At both timepoints, participants wore an ActiGraph accelerometer for 7 days to measure light and moderate-to-vigorous physical activity (MVPA) and an activPAL accelerometer for daily steps. We used analysis of covariance to compare PRO change scores (dependent variables: PCS and MCS, and fatigue) across activity change quartiles (Q). RESULTS:Participants were categorized into Q1 (decreased activity: mean changes = -37.2 minutes/day), Q2 (stable activity: mean change = -4.8 minutes/day), Q3 (modest increase in activity: mean change = 13.2 minutes/day), and Q4 (large increase in activity: mean change = +49.8 minutes/day). For MVPA, participants in Q4 had significantly larger improvements in PCS and MCS compared with those in the lowest quartiles (PCS: Q1 Δ = 1.5 points, P = .026; Q2 Δ = 1.6 points, P = .017; MCS: Q1 Δ = 2.2 points, P = .007). Significant differences also emerged for fatigue as participants in Q4 of MVPA reported improvements in fatigue compared to those in Q1 (Δ = 1.9 points, P = .017) and Q2 (Δ = 1.9 points, P = .016). Improvements in PCS, MCS, and fatigue were observed when comparing the highest quartile of change (Q4) in light intensity activity, daily steps, and MVPA in ≥10-minute bouts to those in Q1 and Q2. CONCLUSIONS:Women with breast cancer who increased physical activity from diagnosis to 1 year had significantly better improvements in PCS, MCS, and fatigue compared with those who decreased or maintained their physical activity.

PURPOSE:Wearable sensors that track physical activity in daily life may offer insights that help health care providers optimize care plans for individuals with cancer. Therefore, we examined the links between lower health-related fitness and worse patient-reported health and various step-based metrics. METHODS:The Alberta Moving Beyond Breast Cancer Study enrolled 1528 women recently diagnosed with breast cancer and measured health-related fitness and patient-reported health outcomes near diagnosis and 1 yr later. Step counts and intensity (cadence, peak steps) were measured by activPAL® over 7 d at baseline. We estimated cross-sectional associations (odds ratios (OR)) at baseline and prospective associations between low baseline stepping and low fitness and poorer health at 1 yr, adjusting for age, demographics, height, weight, and cancer diagnosis/treatment. RESULTS:At baseline, 1408 breast cancer survivors (mean age, 56 yr; early stage (90%)) provided valid activPAL measures (mean, 5.5 d of wear). Taking <5000 steps per day (lower quintile) at baseline was associated with lower aerobic fitness, muscular strength and endurance, lower physical and mental quality of life, and greater fatigue and upper extremity disability at baseline and 1 yr later. Taking <5000 steps per day at baseline was associated with a greater risk of moving from favorable to unfavorable categories of aerobic fitness (OR, 2.64), curlups (OR, 1.84), chest endurance (OR, 2.38), self-reported health (OR, 2.37), physical quality of life (OR, 2.13), and fatigue (OR, 1.81) 1 yr later. Preferred cadence and peak stepping were inconsistently associated after adjustment for total steps. CONCLUSIONS:Although our findings need to be replicated, they suggest that simple step counts measured near diagnosis could help health care providers assess the fitness and health status of women recently diagnosed with breast cancer and improve their survivorship care plans.

BACKGROUND:Administration of chemotherapy during pregnancy is often delayed, while preterm delivery is common. If in utero exposure to chemotherapy is associated with adverse pediatric outcomes, it is unknown whether that relationship is directly attributable to the chemotherapy or is mediated by preterm birth. METHODS:Patients were identified from Canadian cancer registries and administrative data in Alberta, British Columbia, and Ontario, 2003-2017, with follow-up until 2018. The primary exposure was receipt of chemotherapy during pregnancy. Severe neonatal morbidity and mortality (SNM-M), neurodevelopmental disorders and disabilities (NDDs), and pediatric complex chronic conditions (PCCC) reflected short- and long-term pediatric outcomes. Modified Poisson and Cox proportional hazard regression models generated adjusted risk ratios (RR) and hazard ratios (HR), respectively. The influence of preterm birth on the association between exposure to chemotherapy in pregnancy and each study outcome was explored using mediation analysis. RESULTS:Of the 1150 incident cases of cancer during pregnancy, 142 (12.3%) received chemotherapy during pregnancy. Exposure to chemotherapy in pregnancy was associated with a higher risk of SNM-M (RR = 1.67, 95% confidence interval [CI] = 1.13 to 2.46), but not NDD (HR = 0.93, 95% CI = 0.71 to 1.22) or PCCC (HR = 0.96, 95% CI = 0.80 to 1.16). Preterm birth less than 34 and less than 37 weeks mediated 75.8% and 100% of the observed association between chemotherapy and SNM-M, respectively. CONCLUSIONS:Most children born to people with cancer during pregnancy appear to have favorable long-term outcomes, even after exposure to chemotherapy in pregnancy. However, preterm birth is quite common and may contribute to increased rates of adverse neonatal outcomes.

Purpose:To examine the associations between pre-diagnosis exogenous hormone exposure and endogenous sex hormone levels shortly after diagnosis with survival outcomes in endometrial cancer survivors. Methods:In this population-based cohort, females with endometrial cancer were followed from diagnosis to death or January 27, 2022. History of hormone exposure pre-diagnosis and sex-hormone levels shortly after diagnosis were obtained. The associations between hormone exposure and sex-hormone levels with disease-free survival (DFS) and overall survival (OS) were estimated using Cox proportional hazards regression by multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Results:During a median 16.9 years of follow-up (IQR = 15.5-18.1 years), 152 of the 540 participants had a recurrence and/or died. There were no statistically significant associations between exposure to hormonal contraception or menopausal hormone therapy before diagnosis and DFS or OS. Higher estrone levels post-diagnosis were associated with lower DFS (HR 1.56, 95% CI 1.04-2.34) and lower OS (HR 1.76, 95% CI 1.15-2.72). Lower DFS was also observed with higher estradiol levels (HR 1.56, 95% CI 1.02-2.41). Conclusion:There were no associations between pre-diagnosis hormonal contraception or menopausal hormone therapy use and endometrial cancer survival in our study. Endometrial cancer survivors with higher estrogen levels shortly after diagnosis had lower DFS and OS. Further research is needed to confirm these findings.

BACKGROUND:Usual walking pace represents a practical indicator of overall health. However, its association with cancer development remains unexplored. We investigated the relation between self-reported walking pace and cancer risk. METHODS:Using baseline UK Biobank data from 2006 to 2010, excluding the first two years of follow-up to reduce reverse causation, we employed multivariable Cox regression to assess the association between walking pace (slow, steady average, brisk) and risk of 28 cancer types, accounting for overall physical activity and walking volume. RESULTS:After a median follow-up of 10.9 years (interquartile range 10.1-11.8), 8.3% of 334,924 participants received a cancer diagnosis. Brisk compared to slow walking pace was associated with multivariable-adjusted lower risks of five cancers, including anal (hazard ratio 0.30; 95% confidence interval: 0.14-0.63), hepatocellular carcinoma (0.39; 0.23-0.66), small intestine (0.46; 0.24-0.87), thyroid (0.50; 0.29-0.86), and lung cancer (0.60; 0.51-0.70). Our findings were consistent across various sensitivity analyses, which assessed sex and age differences, residual confounding, and reverse causation. CONCLUSIONS:Self-reported walking pace was inversely associated with risk of five cancer types, even when accounting for overall physical activity and walking volume. Adopting a brisk walking pace may represent a pragmatic target for public health interventions to decrease cancer risk, particularly in circumstances where increases in walking volume or frequency prove impractical.

BACKGROUND:There are no studies examining the prospective joint association of device-based measures of sedentary time and physical activity (PA) with cancer mortality. We examined the joint associations of sedentary time and intensity-specific PA with cancer mortality in 72,458 adults from UK Biobank. METHODS:Participants wore an Axivity AX3 accelerometer on their dominant wrist for at least 3 days (with at least 1 weekend day). Cox regression was performed to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for joint associations of sedentary time and intensity-specific PA (light [LPA], moderate [MPA], and vigorous PA [VPA]) with cancer mortality (reference group: high intensity-specific PA and low sedentary time) adjusted for confounders and mutually adjusted for other PA intensities. RESULTS:Associations between sedentary time and cancer mortality were stronger among participants with low PA, irrespective of the intensity. Compared with participants with lower sedentary time (<11 h/d) and high MPA (median of 49 min/d), HR were 1.27 (95% CI, 0.90-1.78) for high sedentary time and high MPA, 1.35 (95% CI, 1.03-1.77) for high sedentary time and medium MPA (49 min/d), and 1.49 (95% CI, 1.15-1.92) for high sedentary time and low MPA (13 min/d). HR for high sedentary time and low light PA (61 min/d) and high sedentary time and low vigorous PA (1 min/d) were 1.25 (95% CI, 1.02-1.59) and 1.57 (95% CI, 1.20-2.06), respectively. CONCLUSIONS:Relatively large amounts of LPA and MPA and small amounts of VPA appeared to attenuate the association between sedentary time and cancer mortality.

BACKGROUND:The American Cancer Society recommends physicians inform average-risk women about endometrial cancer risk on reaching menopause, but new diagnoses are rising fastest in women aged younger than 50 years. Educating these younger women about endometrial cancer risks requires knowledge of risk factors. However, endometrial cancer in young women is rare and challenging to study in single study populations. METHODS:We included 13 846 incident endometrial cancer patients (1639 aged younger than 50 years) and 30 569 matched control individuals from the Epidemiology of Endometrial Cancer Consortium. We used generalized linear models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for 6 risk factors and endometrial cancer risk. We created a risk score to evaluate the combined associations and population attributable fractions for these factors. RESULTS:In younger and older women, we observed positive associations with body mass index and diabetes and inverse associations with age at menarche, oral contraceptive use, and parity. Current smoking was associated with reduced risk only in women aged 50 years and older (Phet < .01). Body mass index was the strongest risk factor (OR≥35 vs<25 kg/m2 = 5.57, 95% CI = 4.33 to 7.16, for ages younger than 50 years; OR≥35 vs<25 kg/m2 = 4.68, 95% CI = 4.30 to 5.09, for ages 50 years and older; Phet = .14). Possessing at least 4 risk factors was associated with approximately ninefold increased risk in women aged younger than 50 years and approximately fourfold increased risk in women aged 50 years and older (Phet < .01). Together, 59.1% of endometrial cancer in women aged younger than 50 years and 55.6% in women aged 50 years and older were attributable to these factors. CONCLUSIONS:Our data confirm younger and older women share common endometrial cancer risk factors. Early educational efforts centered on these factors may help mitigate the rising endometrial cancer burden in young women.

Figure S1 shows the study flowchart for the inclusion of participants. It depicts how we arrived at our final analytic population.

Characteristics of the 27 studies included in the E2C2 pooled analysis

Exercise plays many important roles across the entire cancer continuum that have been described in previous frameworks. These frameworks, however, have generally provided a simplified description of the roles of exercise postdiagnosis. The modern cancer treatment landscape has become complex and often consists of multiple lines of multimodal treatments combined concurrently and/or sequentially and delivered over many months or years. This complexity requires a more multifaceted and targeted approach to the study of exercise after a cancer diagnosis. Here, we propose a new integrated framework—Exercise Across the Postdiagnosis Cancer Continuum (EPiCC)—that highlights the distinct roles of exercise for disease treatment and supportive care from diagnosis until death. We also propose new terminology to clarify the distinct roles of exercise that emerge in the context of the modern cancer treatment landscape. The EPiCC Framework is structured around multiple sequential cancer treatments that highlight six distinct cancer treatment-related time periods for exercise—before treatments, during treatments, between treatments, immediately after successful treatments, during longer term survivorship after successful treatments, and during end of life after unsuccessful treatments. The EPiCC Framework proposes that the specific roles of exercise as a disease treatment and supportive care intervention will vary depending on its positioning within different cancer treatment combinations. As a cancer treatment, exercise may serve as a “priming therapy”, primary therapy, neoadjuvant therapy, induction therapy, “bridging therapy”, adjuvant therapy, consolidation therapy, maintenance therapy, and/or salvage therapy. As a supportive care intervention, exercise may serve as prehabilitation, intrahabilitation, interhabilitation, rehabilitation, “perihabilitation”, health promotion/disease prevention, and/or palliation. To date, exercise has been studied during all of the cancer treatment-related time periods but only in relation to some cancer treatments and combinations. Moreover, fewer studies have examined exercise across multiple cancer treatment-related time periods within any cancer treatment combination. Future research is needed to study exercise as a disease treatment and supportive care intervention within and across the distinct cancer treatment-related time periods contained within different cancer treatment combinations. The aim of the EPiCC Framework is to stimulate a more targeted, integrated, and clinically-informed approach to the study of exercise after a cancer diagnosis.