Christine M. Friedenreich

Introduction: Assessing lifetime physical activity is essential for understanding its cumulative impact on health and ageing; however, no validated instrument is available in Brazilian Portuguese to capture these long-term patterns. The Lifetime Total Physical Activity Questionnaire (LTPAQ) records physical activity across multiple domains and intensities throughout the life course. Objective: To translate the LTPAQ into Brazilian Portuguese, perform a cross cultural validation and evaluate its measurement properties in a population of Brazilian older adults. Methods: This methodological study was conducted in two phases: (1) translation and cross-cultural validation following the Beaton guidelines, and (2) measurement properties according to COSMIN standards. The pre-final version was tested in 30 older adults to assess comprehensibility, and the measurement property analyses were conducted in 80 community-dwelling older adults aged 60–80 years. Test-retest reliability, measurement error (standard error of measurement, Bland–Altman limits of agreement), interpretability (minimum detectable difference, floor and ceiling effects), and hypothesis testing and known-groups analyses for construct validity were evaluated. The calendar method was used to improve lifetime activity recall. Results: The Brazilian Portuguese version of the LTPAQ required minimal cultural adaptation and achieved excellent clarity (content validity index > 0.90). Test-retest reliability was excellent (ICC = 0.89–0.96), with minimal measurement error (SEM = 1%) and low minimum detectable difference values. Narrow limits of agreement were observed for transportation and exercise/sports, while light-to-moderate activities showed wider variability. Floor effects were present in some domains, but no ceiling effects were identified. No significant correlations were observed between the LTPAQ-Brazil and the EuroQol 5-Dimension questionnaire (EQ-5D), the EuroQol Visual Analogue Scale (EQ-VAS), and the International Physical Activity Questionnaire – Short Form (IPAQ-SF). However, significant differences in lifetime physical activity scores were found according to sex, educational attainment, and socioeconomic status, supporting construct validity. Conclusion: The LTPAQ-Brazil demonstrated evidence of cross-cultural validity, reliability, measurement precision, interpretability, and construct validity for assessing lifetime physical activity in Brazilian older adults. The instrument enables the characterization of physical activity exposure across the life course and may be useful for epidemiological and healthy ageing research.

Most physical activity research focuses on general populations, and its cancer-preventive benefits in adults with cardiometabolic diseases remain poorly understood. This study investigated associations between non-occupational physical activity and cancer risk in adults with and without cardiometabolic diseases (cardiovascular disease and/or type 2 diabetes). We conducted a meta-analysis of individual participant data of 598,890 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. Participants with cancer at baseline were excluded. Physical activity was assessed at baseline using self-reported validated questionnaires. We used multivariable-adjusted Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between non-occupational physical activity and the risk of physical activity-related cancers (a composite of 15 cancers), with a multiplicative interaction between non-occupational physical activity and time-varying cardiometabolic disease status. We show that after a median follow-up of 11 years, 37,182 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 increment of non-occupational physical activity is associated with a lower risk of physical activity-related cancer, with HRs of 0.96 (95% CI: 0.93, 0.98) and 0.93 (95% CI: 0.91, 0.96) in adults without and in those with a cardiometabolic disease, respectively (all p-interaction ≥ 0.17). The findings of this study suggest that higher non-occupational physical activity is equally beneficial for cancer prevention in adults with and without cardiometabolic diseases.

Background: Limited research exists on how modifiable lifestyle factors influence tolerability and response to chemotherapy. We investigated the associations between health-related fitness, physical activity, and sedentary behaviour after diagnosis with relative dose intensity (RDI) and pathologic complete response (pCR) among newly diagnosed breast cancer patients who received neoadjuvant or adjuvant chemotherapy. Methods: This analysis includes 890 participants of the Alberta Moving Beyond Breast Cancer prospective cohort study who received chemotherapy. We directly measured cardiorespiratory fitness, muscular strength and endurance, body composition, physical activity, sedentary behaviour shortly after diagnosis and abstracted RDI and pCR data from medical charts. We used logistic regression to measure the associations with RDI ( < 85%, ≥ 85%) and pCR (no, yes). Results: Of 890 participants, 726 (81.6%) achieved ≥85% RDI. We found negative linear associations between ≥ 85% RDI and greater body mass index (BMI), waist circumference, waist-to-hip ratio and fat mass percentage; and positive linear associations for greater lean body mass percentage and lean-to-fat mass ratio. We observed positive dose-response relationships between ≥ 85% RDI and relative VO _2peak , upper body and lower body strength. Higher lean-to-fat mass ratio was positively associated with pCR, in contrast to negative associations for BMI and self-reported physical activity. Conclusion: Greater relative aerobic fitness, muscular strength, and healthy body composition were consistently associated with better chemotherapy tolerance whereas fewer associations were found with chemotherapy response.

Background: Moderate-to-vigorous physical activity (MVPA) is inversely associated with risks of cancer, cardiovascular diseases (CVD), type 2 diabetes (T2D), and their co-occurrence, defined as multimorbidity; however, the underlying biological pathways remain unclear. Methods: In 33,806 UK Biobank participants with 2911 measured blood proteins, a proteomic signature of MVPA was derived with linear and LASSO regressions. Multivariable Cox models, adjusted for MVPA, estimated prospective associations with cancer, CVD, T2D, and multimorbidity. Results: We show that after multiple testing corrections, 220 proteins are retained in the MVPA signature. Proteins related to food intake, metabolism, and cell growth (e.g., LEP, MSTN) are inversely associated, while those involved in immune cell migration and musculoskeletal integrity (e.g., integrins, COMP) are positively associated with MVPA. Several proteins positively associated with MVPA are inversely associated with disease risk (e.g., integrins, CLEC4A for cancer; LPL, LEP for T2D), while proteins negatively associated with MVPA are positively associated with disease risk (e.g., CD38, TGFA for CVD). The proteomic signature score is inversely associated with cancer risk (hazard ratio per interquartile range: 0.87; 95% confidence interval: 0.78, 0.96) and T2D (0.66; 0.60, 0.72). For multimorbidity, proteins inversely related to MVPA align with expected risk patterns (e.g., GGT1, HR: 1.32; 95% CI: 1.12, 1.57), but the proteomic signature score is not associated. Conclusions: This study identifies several proteins associated with MVPA that are also associated with cancer, CVD, T2D, and the multimorbidity of these conditions. Further studies investigating the causal nature of these associations are welcome.

Background: Sleep problems are common among breast cancer survivors and are associated with poor quality of life. However, few studies have considered whether depressive symptoms confound or modify this association. This study evaluates whether depressive symptoms attenuate the association between sleep and quality of life in newly diagnosed breast cancer survivors. Methods: Women with newly diagnosed early‐stage breast cancer were recruited between 2012 and 2019 in Alberta, Canada, and completed the Pittsburg Sleep Quality Index (PSQI) to characterize global sleep quality and subscales. Quality of life was measured using the Short Form Survey (SF‐36 version‐2) to assess physical and mental well‐being. Depressive symptoms were measured using the Patient Health Questionnaire (PHQ‐9). Multivariable linear regressions were used to estimate the association of sleep characteristics with physical and mental well‐being. Depressive symptoms were evaluated as a potential confounder and effect modifier. Results: Among 1454 breast cancer survivors with available data, 43% reported poor global sleep quality and 10.5% reported clinically meaningful depressive symptoms. Poor sleep quality was associated with lower physical ( β = −3.0, 95% CI: −3.8 to −2.3) and mental well‐being ( β = −5.7, 95% CI: −6.7 to −4.7). These associations were attenuated to ( β = −2.3, 95% CI: −3.1 to 1.5) and ( β = −1.2, 95% CI: −2.1 to −0.3) after further adjusting for depressive symptoms. Stratified analyses showed slightly stronger associations in women with non‐minimal depressive symptoms, though this association was not clinically meaningful. Conclusion: The association between sleep and quality of life was substantially attenuated after accounting for depressive symptoms. Longitudinal data are needed to clarify whether depressive symptoms confound, mediate, or modify this relationship to better guide targeted interventions in breast cancer survivorship.

Adjuvant therapies are provided to endometrial cancer patients with advanced risk and may impact the associations of lifestyle with survival. We examined the long‐term associations of physical activity (PA) with survival outcomes in endometrial cancer survivors by primary cancer treatment. Women with endometrial cancer who underwent hysterectomy ( N = 527) in Alberta, Canada between 2002 and 2006 recalled their lifetime pre‐diagnosis PA shortly after diagnosis and their PA since diagnosis at 3.4 years follow‐up using the Lifetime Total PA Questionnaire. Vital status was obtained through record linkage from Alberta Health Services, while recurrences and second primary cancers were abstracted from medical records. Cox proportional hazards models were used to examine interactions between PA and primary treatment (surgery alone vs. surgery plus adjuvant therapy) for overall survival (OS) and disease‐free survival (DFS). Of 527 survivors, 333 underwent surgery alone and 194 underwent surgery plus adjuvant therapy. Over 16.7 years, 128 deaths and 194 DFS events occurred. For DFS, meeting PA guidelines pre‐diagnosis (interaction p = .035) was associated with lower events in surgery alone but with higher events in surgery plus adjuvant therapy. Although other interactions between treatment regimen and PA were not statistically significant, overall, increasing PA showed lower risks of OS and DFS events in the surgery alone group, but showed higher risks in the surgery plus adjuvant therapy group. Associations between PA and survival may differ by primary treatment, with generally protective associations in the surgery alone group and harmful associations in the surgery plus adjuvant therapy.

Background: Colon Health and Life-Long Exercise Change (CHALLENGE) was the first phase 3 trial to examine the effects of exercise on cancer-related survival and, therefore, required a substantial and sustained increase in moderate-to-vigorous physical activity (MVPA) that had not been achieved in previous trials. Here, we report the effects of the intervention on the social cognitive beliefs that were targeted to achieve long-term exercise behavior change. Methods: Patients with resected colon cancer who had completed chemotherapy were randomized to health education materials (HEM) or a structured exercise program (SEP) consisting of 48 behavioral support sessions delivered over a 3-year period. Social cognitive constructs from the Theory of Planned Behavior were assessed by single items using 5-point scales at baseline and every 6 months during the 3-year intervention. Regression models for repeated measurements were used to estimate the least square means and robust standard errors (SEs) for each randomized group at each time point. Results: Between 2009 and 2024, 889 patients were randomized to SEP (n = 445) or HEM (n = 444). SEP compared to HEM reported significantly more favorable social cognitive beliefs about exercise at almost all time points. Average intervention effects (AIE) across the 3-year intervention favored SEP for perceived benefit (AIE = 0.29; P < .001), enjoyment (AIE = 0.40; P < .001), difficulty (AIE = −0.18; P = .003), confidence (AIE = 0.28; P < .001), support (AIE = 0.59; P < .001), motivation (AIE = 0.47; P < .001), opportunity (AIE = 0.31; P < .001), and planning (AIE = 0.82; P < .001). All social cognitive variables were significantly associated with self-reported MVPA at all time points. Conclusions: The SEP intervention in the CHALLENGE trial successfully targeted the social cognitive beliefs that were associated with sustained MVPA. NCT00819208.

Background/Objectives: Early-stage breast cancer treatments adversely affect components of health-related fitness (HRF) important for treatment tolerability, recovery, and long-term outcomes. Few studies have examined cancer treatment modality-specific effects on HRF. We examined associations of breast cancer treatment modalities, regimens, and combinations with one-year changes in HRF. Methods: Newly diagnosed early-stage breast cancer patients were recruited between 2012 and 2019 for the Alberta Moving Beyond Breast Cancer (AMBER) cohort study. HRF assessments were completed within 90 days of diagnosis and at one year, including cardiorespiratory fitness, muscle strength and endurance, and body composition. Analysis of covariance was used to test whether HRF changes differed between treatment modalities, regimens, and combinations. All tests were 2-sided. Results: A total of 1350 participants (mean [SD] age, 55.6 [10.7] years) were included. Women who received chemotherapy (n = 797; 59%) experienced statistically significant smaller increases in upper body strength (−1.7 kg, 95% confidence interval [CI]: −3.0 to −0.5), greater declines in lower body endurance (−118.0 kg, 95%CI: −216.6 to −19.3), and greater declines in total lean mass (−0.7 kg, 95%CI: −1.1 to −0.3), bone mineral density (−0.01 g/cm², 95%CI: −0.02 to 0.00), and bone mineral content (0.04 kg, 95%CI: −0.06 to −0.02). Other treatment modalities were modestly and inconsistently associated with HRF changes. Treatment combinations that included chemotherapy had the most negative impact on cardiorespiratory fitness and body composition. Conclusions: Chemotherapy—either alone or in combination with other treatments—had the largest and broadest negative impact on HRF recovery in early-stage breast cancer at one-year follow-up.

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.