Dose-response effects of aerobic exercise on energy compensation in postmenopausal women: combined results from two randomized controlled trials.

BACKGROUND/OBJECTIVES: Despite the clear health benefits of exercise, exercised-induced weight loss is often less than expected. The term 'exercise energy compensation' is used to define the amount of weight loss below what is expected for the amount of exercise energy expenditure. We examined the dose-response effects of exercise volume on energy compensation in postmenopausal women. PARTICIPANTS/METHODS: Data from Alberta Physical Activity and Breast Cancer Prevention (ALPHA) and Breast Cancer and Exercise Trial in Alberta (BETA) were combined for the present analysis. The ALPHA and BETA trials were two-centred, two-armed, 12-month randomized controlled trials. The ALPHA trial included 160 participants randomized to 225 min per week of aerobic exercise, and the BETA trial randomized 200 participants to each 150 and 300 min per week of aerobic exercise. All participants were aged 50-74 years, moderately inactive (<90 min per week of exercise), had no previous cancer diagnosis and a body mass index between 22 and 40 kg m-2. Energy compensation was based on changes in body composition (dual-energy X-ray absorptiometry scan) and estimated exercise energy expenditure from completed exercise volume. Associations between Δenergy intake, ΔVO2peak and Δphysical activity time with energy compensation were assessed. RESULTS: No differences in energy compensation were noted between interventions. However, there were large inter-individual differences in energy compensation between participants; 9.4% experienced body composition changes that were greater than expected based on exercise energy expenditure, 64% experienced some degree of energy compensation and 26.6% experienced weight gain based on exercise energy expenditure. Increases in VO2peak were associated with reductions in energy compensation (ß=-3.44 ml kg-1 min-1, 95% confidence interval for ß=-4.71 to -2.17 ml kg-1 min-1; P=0.0001). CONCLUSIONS: Large inter-individual differences in energy compensation were noted, despite no differences between activity doses. In addition, increases in VO2peak were associated with lower energy compensation. Future studies are needed to identify behavioral and metabolic factors that may contribute to this large inter-individual variability in energy compensation.

Infertility and incident endometrial cancer risk: a pooled analysis from the epidemiology of endometrial cancer consortium (E2C2).

BACKGROUND: Nulliparity is an endometrial cancer risk factor, but whether or not this association is due to infertility is unclear. Although there are many underlying infertility causes, few studies have assessed risk relations by specific causes. METHODS: We conducted a pooled analysis of 8153 cases and 11 713 controls from 2 cohort and 12 case-control studies. All studies provided self-reported infertility and its causes, except for one study that relied on data from national registries. Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Nulliparous women had an elevated endometrial cancer risk compared with parous women, even after adjusting for infertility (OR=1.76; 95% CI: 1.59-1.94). Women who reported infertility had an increased risk compared with those without infertility concerns, even after adjusting for nulliparity (OR=1.22; 95% CI: 1.13-1.33). Among women who reported infertility, none of the individual infertility causes were substantially related to endometrial cancer. CONCLUSIONS: Based on mainly self-reported infertility data that used study-specific definitions of infertility, nulliparity and infertility appeared to independently contribute to endometrial cancer risk. Understanding residual endometrial cancer risk related to infertility, its causes and its treatments may benefit from large studies involving detailed data on various infertility parameters.

Subgroup effects in a randomised trial of different types and doses of exercise during breast cancer chemotherapy.

BACKGROUND: The Combined Aerobic and Resistance Exercise Trial tested different types and doses of exercise in breast cancer patients receiving chemotherapy. Here, we explore potential moderators of the exercise training responses. METHODS: Breast cancer patients initiating chemotherapy (N=301) were randomly assigned to three times a week, supervised exercise of a standard dose of 25-30 min of aerobic exercise, a higher dose of 50-60 min of aerobic exercise, or a higher dose of 50-60 min of combined aerobic and resistance exercise. Outcomes were patient-reported symptoms and health-related fitness. Moderators were baseline demographic, exercise/fitness, and cancer variables. RESULTS: Body mass index moderated the effects of the exercise interventions on bodily pain (P for interaction=0.038), endocrine symptoms (P for interaction=0.029), taxane/neuropathy symptoms (P for interaction=0.013), aerobic fitness (P for interaction=0.041), muscular strength (P for interaction=0.007), and fat mass (P for interaction=0.005). In general, healthy weight patients responded better to the higher-dose exercise interventions than overweight/obese patients. Menopausal status, age, and baseline fitness moderated the effects on patient-reported symptoms. Premenopausal, younger, and fitter patients achieved greater benefits from the higher-dose exercise interventions. CONCLUSIONS: Healthy weight, fitter, and premenopausal/younger breast cancer patients receiving chemotherapy are more likely to benefit from higher-dose exercise interventions.

Physical activity, sex steroid, and growth factor concentrations in pre- and post-menopausal women: a cross-sectional study within the EPIC cohort.

PURPOSE: Increased physical activity (PA) is associated with a reduced risk of several cancers. PA may reduce cancer risk by changing endogenous hormones levels, but relatively little research has focused on this topic. The purpose of this study was to elucidate the relation between PA and endogenous hormone concentrations. METHODS: A cross-sectional analysis of 798 pre- and 1,360 post-menopausal women included as controls in case-control studies on endogenous hormones (steroids, progesterone, sex-hormone-binding globulin (SHBG), and growth factors) levels, and cancer risk nested within European Prospective Investigation into Cancer and Nutrition cohort was performed. Multivariate regression analyses were performed to compare geometric mean levels of hormones and SHBG by categories of PA. RESULTS: In pre-menopausal women, active women had 19 % significantly lower concentrations of androstenedione, 14 % lower testosterone, and 20 % lower free testosterone than inactive women, while no differences were observed for estrogens, progesterone, SHBG, and growth factors. In post-menopausal women, active women had 18 % significantly lower estradiol and 20 % lower free estradiol concentrations than inactive women, while no differences were observed for the other hormones and SHBG. More vigorous forms of physical activity were associated with higher insulin-like growth factor-I concentrations. Adjustment for body mass index did not alter the associations. Overall, the percentage of variance in hormone concentrations explained by PA levels was <2 %. CONCLUSIONS: Our results support the hypothesis of an influence, although small in magnitude, of PA on sex hormone levels in blood, independent of body size.

The etiology of uterine sarcomas: a pooled analysis of the epidemiology of endometrial cancer consortium.

BACKGROUND: Uterine sarcomas are characterised by early age at diagnosis, poor prognosis, and higher incidence among Black compared with White women, but their aetiology is poorly understood. Therefore, we performed a pooled analysis of data collected in the Epidemiology of Endometrial Cancer Consortium. We also examined risk factor associations for malignant mixed mullerian tumours (MMMTs) and endometrioid endometrial carcinomas (EECs) for comparison purposes. METHODS: We pooled data on 229 uterine sarcomas, 244 MMMTs, 7623 EEC cases, and 28,829 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) for risk factors associated with uterine sarcoma, MMMT, and EEC were estimated with polytomous logistic regression. We also examined associations between epidemiological factors and histological subtypes of uterine sarcoma. RESULTS: Significant risk factors for uterine sarcoma included obesity (body mass index (BMI)≥30 vs BMI<25 kg m(-2) (OR: 1.73, 95% CI: 1.22-2.46), P-trend=0.008) and history of diabetes (OR: 2.33, 95% CI: 1.41-3.83). Older age at menarche was inversely associated with uterine sarcoma risk (≥15 years vs <11 years (OR: 0.70, 95% CI: 0.34-1.44), P-trend: 0.04). BMI was significantly, but less strongly related to uterine sarcomas compared with EECs (OR: 3.03, 95% CI: 2.82-3.26) or MMMTs (OR: 2.25, 95% CI: 1.60-3.15, P-heterogeneity=0.01). CONCLUSION: In the largest aetiological study of uterine sarcomas, associations between menstrual, hormonal, and anthropometric risk factors and uterine sarcoma were similar to those identified for EEC. Further exploration of factors that might explain patterns of age- and race-specific incidence rates for uterine sarcoma are needed.

Medical, demographic and social cognitive correlates of physical activity in a population-based sample of colorectal cancer survivors.

Physical activity (PA) improves quality of life in colorectal cancer survivors (CRC) and may reduce the risk of disease recurrence and early death. Few studies, however, have examined the correlates of PA in CRC survivors. Using the Alberta Cancer Registry, 2000 randomly selected CRC survivors were mailed a self-reported questionnaire assessing medical, demographic, behavioural and social cognitive variables from the theory of planned behaviour (TPB). Of the 600 survivors who responded, 33% were meeting public health PA guidelines and almost half were completely sedentary. Higher PA was reported by survivors who were younger, unmarried, better educated, wealthier, employed, non-smokers, social drinkers, not treated with radiation therapy, disease-free, in better health and less comorbidity. In multivariate path analysis, these variables were not directly associated with PA after controlling for the TPB variables. The TPB explained 34% (P < 0.001) of the variance in PA behaviour with direct associations for intention (ß= 0.22; P= 0.015) and planning (ß= 0.18; P= 0.001). Intention, in turn, had 62% (P < 0.001) of its variance explained by perceived behavioural control (ß= 0.43; P < 0.001), affective attitude (ß= 0.25; P < 0.001) and instrumental attitude (ß= 0.15; P < 0.001). The TPB may be a useful framework for developing population-based interventions to increase PA in CRC survivors.

Adiposity changes after a 1-year aerobic exercise intervention among postmenopausal women: a randomized controlled trial.

OBJECTIVE: We examined the effects of an aerobic exercise intervention on adiposity outcomes that may be involved in the association between physical activity and breast cancer risk. DESIGN: This study was a two-centre, two-armed, randomized controlled trial. The 1-year-long exercise intervention included 45 min of moderate-to-vigorous aerobic exercise five times per week, with at least three of the sessions being facility based. The control group was asked not to change their activity and both groups were asked not to change their diet. SUBJECTS: A total of 320 postmenopausal, sedentary, normal weight-to-obese women aged 50-74 years who were cancer-free, nondiabetic and nonhormone replacement therapy users were included in this study. MEASUREMENTS: Anthropometric measurements of height, weight and waist and hip circumferences; dual energy X-ray absorptiometry measurements of total body fat; and computerized tomography measurements of abdominal adiposity were carried out. RESULTS: Women in the exercise group exercised a mean of 3.6 days (s.d.=1.3) per week and 178.5 min (s.d.=76.1) per week. Changes in all measures of adiposity favored exercisers relative to controls (P<0.001). The mean difference between groups was: -1.8 kg for body weight; -2.0 kg for total body fat; -14.9 cm(2) for intra-abdominal fat area; and -24.1 cm(2) for subcutaneous abdominal fat area. A linear trend of greater body fat loss with increasing volume of exercise was also observed. CONCLUSION: A 1-year aerobic exercise program consistent with current public health guidelines resulted in reduced adiposity levels in previously sedentary postmenopausal women at higher risk of breast cancer.

A pan-Canadian prospective study of young women with breast cancer: the rationale and protocol design for the RUBY study.

Introduction: The understanding of the biology and epidemiology of, and the optimal therapeutic strategies for, breast cancer (bca) in younger women is limited. We present the rationale, design, and initial recruitment of Reducing the Burden of Breast Cancer in Young Women (ruby), a unique national prospective cohort study designed to examine the diagnosis, treatment, quality of life, and outcomes from the time of diagnosis for young women with bca. Methods: Over a 4-year period at 33 sites across Canada, the ruby study will use a local and virtual recruitment model to enrol 1200 women with bca who are 40 years of age or younger at the time of diagnosis, before initiation of any treatment. At a minimum, comprehensive patient, tumour, and treatment data will be collected to evaluate recurrence and survival. Patients may opt to complete patient-reported questionnaires, to provide blood and tumour samples, and to be contacted for future research, forming the core dataset from which 4 subprojects evaluating genetics, lifestyle factors, fertility, and local management or delivery of care will be performed. Summary: The ruby study will be the most comprehensive repository of data, biospecimens, and patient-reported outcomes ever collected with respect to young women with bca from the time of diagnosis, enabling research unique to that population now and into the future. This research model could be used for other oncology settings in Canada.

The Dietary Inflammatory Index® and Alternative Healthy Eating Index 2010 in relation to leucocyte telomere length in postmenopausal women: a cross-sectional study.

Telomeres are nucleoprotein complexes that form the ends of eukaryotic chromosomes where they protect DNA from genomic instability, prevent end-to-end fusion and limit cellular replicative capabilities. Increased telomere attrition rates, and relatively shorter telomere length, is associated with genomic instability and has been linked with several chronic diseases, malignancies and reduced longevity. Telomeric DNA is highly susceptible to oxidative damage and dietary habits may make an impact on telomere attrition rates through the mediation of oxidative stress and chronic inflammation. The aim of this study was to examine the association between leucocyte telomere length (LTL) with both the Dietary Inflammatory Index® 2014 (DII®) and the Alternative Healthy Eating Index 2010 (AHEI-2010). This is a cross-sectional analysis using baseline data from 263 postmenopausal women from the Alberta Physical Activity and Breast Cancer Prevention (ALPHA) Trial, in Calgary and Edmonton, Alberta, Canada. No statistically significant association was detected between LTL z-score and the AHEI-2010 (P = 0·20) or DII® (P = 0·91) in multivariable adjusted models. An exploratory analysis of AHEI-2010 and DII® parameters and LTL revealed anthocyanidin intake was associated with LTL (P < 0·01); however, this association was non-significant after a Bonferroni correction was applied (P = 0·27). No effect modification by age, smoking history, or recreational physical activity was detected for either relationship. Increased dietary antioxidant and decreased oxidant intake were not associated with LTL in this analysis.

Physical activity and breast cancer risk: impact of timing, type and dose of activity and population subgroup effects.

OBJECTIVE: To review (1) the epidemiological literature on physical activity and the risk of breast cancer, examining the effect of the different parameters of activity and effect modification within different population subgroups; and (2) the biological mechanisms whereby physical activity may influence the risk of breast cancer. METHODS: A review of all published literature to September 2007 was conducted using online databases; 34 case-control and 28 cohort studies were included. The impact of the different parameters of physical activity on the association between activity and the risk of breast cancer was examined by considering the type of activity performed, the timing of activity over the life course and the intensity of activity. Effect modification of this association by menopausal status, body mass index (BMI), racial group, family history of breast cancer, hormone receptor status, energy intake and parity were also considered. RESULTS: Evidence for a risk reduction associated with increased physical activity was found in 47 (76%) of 62 studies included in this review with an average risk decrease of 25-30%. A dose-response effect existed in 28 of 33 studies. Stronger decreases in risk were observed for recreational activity, lifetime or later life activity, vigorous activity, among postmenopausal women, women with normal BMI, non-white racial groups, those with hormone receptor negative tumours, women without a family history of breast cancer and parous women. CONCLUSIONS: The effect of physical activity on the risk of breast cancer is stronger in specific population subgroups and for certain parameters of activity that need to be further explored in future intervention trials.

The Colon Health and Life-Long Exercise Change trial: a randomized trial of the National Cancer Institute of Canada Clinical Trials Group.

BACKGROUND: Observational studies indicate that physical activity (PA) is strongly associated with improved disease outcomes in colon cancer survivors, but a randomized controlled trial is needed to determine whether the association is causal and whether new policies to promote exercise are justified. PURPOSE: The co.21 Colon Health and Life-Long Exercise Change (challenge) trial undertaken by the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) is designed to determine the effects of a structured pa intervention on outcomes for survivors of high-risk stage II or III colon cancer who have completed adjuvant therapy within the previous 2-6 months. METHODS: Trial participants (n = 962) will be stratified by centre, disease stage, body mass index, and performance status, and will be randomly assigned to a structured pa intervention or to general health education materials. The pa intervention will consist of a behavioural support program and supervised pa sessions delivered over a 3-year period, beginning with regular face-to-face sessions and tapering to less frequent face-to-face or telephone sessions. The primary endpoint is disease-free survival. Important secondary endpoints include multiple patient-reported outcomes, objective physical functioning, biologic correlative markers, and an economic analysis. SUMMARY: Cancer survivors and cancer care professionals are interested in the potential role of PA to improve multiple disease-related outcomes, but a randomized controlled trial is needed to provide compelling evidence to justify changes in health care policies and practice.

Role of exercise training in polycystic ovary syndrome: a systematic review and meta-analysis.

Preliminary evidence suggests exercise in polycystic ovary syndrome (PCOS) may improve reproductive and cardiometabolic parameters. Our primary aim was to determine the impact of exercise training on reproductive health in women with PCOS. Our secondary aim was to determine the effect of exercise training on cardiometabolic indices. A systematic review of published literature was conducted using MEDLINE and EMBASE based on a pre-published protocol (PROSPERO CRD42017065324). The search was not limited by year. Randomized controlled trials, non-randomized controlled trials and uncontrolled trials that evaluated an exercise intervention in women with PCOS and reported reproductive outcomes were included. Reproductive outcomes were analysed semi-quantitatively and a meta-analysis was conducted for reported cardiometabolic outcomes. Of 517 screened abstracts, 14 studies involving 617 women with PCOS were included: seven randomized controlled trials, one non-randomized controlled trial and six uncontrolled trials. There were insufficient published data to describe the effect of exercise interventions on ovulation quantitatively, but semi-quantitative analysis suggested that exercise interventions may improve menstrual regularity, pregnancy and ovulation rates. Our meta-analysis found that exercise improved lipid profiles and decreased waist circumference, systolic blood pressure and fasting insulin. The impact of exercise interventions on reproductive function remains unclear. However, our meta-analysis suggests that exercise interventions may improve cardiometabolic profiles in women with PCOS.

A cohort study of fat intake and risk of breast cancer.

Between 1982 and 1987, 519 newly incident, histologically confirmed cases of breast cancer were identified in a cohort of 56,837 women enrolled in the Canadian National Breast Screening Study. These women had completed a dietary questionnaire before the occurrence of their breast cancer, and this has been used to estimate their intake of dietary fat and several other nutrients. There is evidence of a positive association between breast cancer and total fat intake, with a relative risk of 1.35 (95% confidence interval, 1.00-1.82) per 77 g per day, and some evidence of a dose-response relationship (P = .052).

Methodologic issues for pooling dietary data.

This paper presents the methodologic issues to consider when conducting a pooled analysis of data from nutritional epidemiologic studies. Because a wide variety of dietary assessment methods have been used in nutritional epidemiology, pooled analyses often combine data collected under very different circumstances. Whether these different methods influence the results obtained in a pooled analysis has not yet been examined. One of the main concerns in a pooled analysis is whether the data to be pooled are comparable. Questions to consider regarding data comparability and methods to address these questions in a pooled analysis are discussed.

Physical activity and cancer prevention: from observational to intervention research.

The purpose of this review is to articulate how progress in epidemiological research on physical activity and cancer prevention can be made. This report briefly reviews the accumulated evidence for an etiological role of physical activity in the prevention of cancer of the colon, breast, prostate, testes, lung, endometrium, and ovary and summarizes the evidence for a causal association for each of these sites. The evidence for a causal association between physical activity and colon and breast cancers is found to be "convincing," for prostate cancer to be "probable," for lung and endometrial cancers to be "possible," and for testicular and ovarian cancers to be currently "insufficient" to make any definitive conclusions. The emerging literature on physical activity and cancer prevention intervention studies is presented, and an overview of the literature on physical activity intervention is also provided. Given the level of evidence that is currently available for the associations between physical activity and cancer, it is argued that for additional progress to be made in this field, there need to be intervention studies on physical activity and cancers of the colon and breast. For the remaining cancer sites, better designed observational epidemiological studies are needed that address the identified methodological limitations found in previous studies. These limitations include crude and incomplete physical activity assessment, lack of adequate control for confounding and effect modification, as well as a lack of consideration of the underlying biological mechanisms that are operative. This review concludes with detailed recommendations for future research in this field.

An investigation of recall bias in the reporting of past food intake among breast cancer cases and controls.

A nested case-control study was conducted within the Canadian National Breast Screening Study to examine whether there was evidence for biased reporting of past food intake. A total of 325 case patients with breast cancer and 628 matched control subjects completed a self-administered food frequency questionnaire in 1988, recalling their diets originally reported on enrollment into the National Breast Screening Study between 1982 and 1985. Recall of food items was very similar for case patients and control subjects. The magnitude of the odds ratios for the association between these food groups and breast cancer from the prospectively and retrospectively collected data was not systematically different. There was little evidence for recall bias in the reporting of past food intake from these data.

Recall bias in the association of micronutrient intake and breast cancer.

A nested case-control study within the Canadian National Breast Screening Study was conducted to examine whether there was evidence for recall bias in the reporting of past micronutrient intake. Dietary data collected upon enrollment between 1982 and 1985 from 325 breast cancer cases and 628 matched controls were compared with data collected in 1988 after disease diagnosis. The retrospective estimates of mean micronutrient intakes from food sources were found to be very similar to the prospective estimates for cases and controls. Errors of omission and commission for the reporting of previous supplementary vitamin use were identical for both subject groups. The odds ratios estimated for the association of micronutrient intake and breast cancer for the prospective and retrospective data were similar in magnitude and the 95% confidence intervals overlapped considerably. There was no evidence for recall bias in the estimation of past micronutrient intake by breast cancer cases as compared to controls.

Physical activity and cancer: lessons learned from nutritional epidemiology.

Convincing epidemiologic evidence currently exists for an association between physical activity and the prevention of colon and breast cancer Physical activity may also reduce the risk of cancer at several other sites. With increasing research on this topic, it is apparent that studies of physical activity and cancer have numerous methodological similarities with studies of nutrition and cancer Lessons learned from nutritional epidemiology that can be applied to studies of physical activity and cancer prevention and recommendations for future research are discussed in this review.

Review of anthropometric factors and breast cancer risk.

Epidemiological evidence implicating anthropometric risk factors in breast cancer aetiology is accumulating. For premenopausal women, breast cancer risk increases with increasing height, but decreases with higher weight or body mass index, and no association with increased central adiposity exists. For postmenopausal women, an increased risk of breast cancer is found with increasing levels of all the anthropometric variables including height, weight, body mass index, waist-hip ratio, waist circumference and weight gain. Weight loss appears to decrease risk, particularly if it occurs later in life. Breast size may be a risk factor for breast cancer, however, the current evidence is inconclusive. Several hypothesized biologic mechanisms exist to explain how anthropometric factors influence breast cancer risk. Obesity may increase levels of circulating endogenous sex hormones, insulin and insulin-like growth factors that all, in turn, increase breast cancer risk. Genetic predisposition to obesity and to specific body fat distributions are also implicated. With obesity, there are increased levels of fat tissue that can store toxins and can serve as a continuous source of carcinogens. Recommendations for future research on anthropometric factors and breast cancer are provided. Sufficient evidence exists to support strategies to avoid weight gain throughout life as a means of reducing postmenopausal breast cancer risk.

Physical activity and risk of breast cancer.

The association between recreational physical activity and breast cancer risk was examined in a population-based case-control study in Adelaide, Australia between 1982 and 1984. There were 451 incident, histologically confirmed cases of breast cancer, identified through the South Australian Central Cancer Registry, which were each age-matched to one control selected at random from the electoral register. These women, aged 20-74 years at diagnosis, reported their level of weekly recreational physical activity in a self-administered questionnaire. The questionnaire reports of light, moderate and vigorous physical activity were converted into total kilocalories per week of energy expenditure. A decrease in risk of breast cancer was found with increasing levels of total recreational physical activity (P (trend) = 0.09). The adjusted odds ratio for those women who expended more than 4,000 kcal/week was 0.73 (95% confidence interval (CI) 0.51-1.05) compared with women who undertook no physical activity. The reduction in risk with recreational physical activity was most evident for women who undertook any vigorous activity. These results provide some support for the hypothesis that physical activity may decrease the risk of developing breast cancer.