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1.  Biobehavioral Factors Mediate Exercise Effects on Fatigue in Breast Cancer Survivors 
Purpose
Examine mediators of fatigue response to an exercise intervention for breast cancer survivors (BCS) in a pilot randomized controlled trial.
Methods
Postmenopausal BCS (n=46; ≤ Stage II), off primary treatment, and reporting fatigue and/or sleep dysfunction were randomized to a 3-month exercise intervention (160 minutes/week of moderate intensity aerobic walking, twice weekly resistance training with resistance bands) or control group. Six discussion group sessions provided behavioral support to improve adherence. Fatigue, serum cytokines, accelerometer physical activity, cardiorespiratory fitness, sleep dysfunction, and psychosocial factors were assessed at baseline and 3 months.
Results
Exercise intervention effect sizes for fatigue were: fatigue intensity d=0.30 (p=.34), interference d=−0.38 (p=.22), and general fatigue d=−0.49 (p=.13). Using Freedman-Schatzkin difference-in-coefficients tests, increase in fatigue intensity was significantly mediated by interleukin (IL)-6 (82%), IL-10 (94%), IL-6:IL-10 (49%), and tumor necrosis factor (TNF)-alpha:IL-10 (78%) with reduced sleep dysfunction increasing the relationship between intervention and fatigue intensity rather than mediating intervention effects (−88%). Decrease in fatigue interference was mediated by sleep dysfunction (35%) while IL-10 and pro:anti-inflammatory cytokine ratios increased the relationship between intervention and interference (−25% to −40%). The reduction in general fatigue was significantly mediated by minutes of physical activity (76%), sleep dysfunction (45%), and physical activity enjoyment (40%) with IL-10 (−40%) and IL-6:IL-10 (−11%) increasing the intervention-fatigue relationship. In the intervention group, higher baseline fatigue, anxiety, depression, and perceived exercise barriers interference predicted a greater decline in fatigue interference and/or general fatigue during the intervention.
Conclusions
Biobehavioral factors mediated and enhanced intervention effects on fatigue while psychosocial factors predicted fatigue response. Further study is warranted to confirm our results and improve understanding of relationships that mediate and strengthen the intervention-fatigue association.
doi:10.1249/MSS.0000000000000210
PMCID: PMC4435796  PMID: 24212124
oncology; prevention; determinants; survivorship; predictors
2.  Predictors of physical activity at 12 month follow-up after a supervised exercise intervention in postmenopausal women 
Background
Few studies have examined recreational physical activity (RPA) after participating in a structured exercise intervention. More specifically, little is known about the long-term effects of exercise interventions in post-menopausal women. This study had two objectives: 1) To compare RPA in postmenopausal women in the exercise group and the control group 12 months after the end of the Alberta Physical Activity and Breast Cancer Prevention (ALPHA) Trial; and 2) To apply the Theory of Planned Behaviour (TPB) to identify predictors of RPA 12 months post-intervention among women in the exercise group.
Methods
Self-reported RPA 12-months post-intervention from a validated questionnaire was used to estimate RPA levels for control group (118/160, 74% response) and exercise group participants (126/160, 79% response). Bivariate analysis was used to compare RPA between exercise and control group participants and to identify TPB variables for multivariate analysis. Logistic regression was applied to TPB data collected from self- administered questionnaires at end of trial by exercise group participants (126/160, 79% response) to identify predictors of long-term RPA.
Results
At 12 months post-intervention, 62% of women in the exercise group were active compared to 58% of controls (p = 0.52). Of the TPB constructs examined, self-efficacy (OR =2.98 (1.08-8.20)) and behavioural beliefs (OR = 1.46 (1.03-2.06)) were identified as predictors of RPA for exercise group participants.
Conclusions
Levels of RPA in the exercise and control groups were comparable 12 months post intervention, indicating that participation in the ALPHA trial was associated with increased physical activity in previously inactive women, regardless of randomization into either the exercise group or in the control group. Exercise interventions that promote self-efficacy and positive behavioural beliefs have the potential to have long-term impacts on physical activity behaviour, although further research is needed to examine additional psychological, social and environmental predictors of long-term RPA in post-menopausal women.
Trial registration
ClinicalTrials.gov NCT00522262.
Electronic supplementary material
The online version of this article (doi:10.1186/s12966-015-0219-z) contains supplementary material, which is available to authorized users.
doi:10.1186/s12966-015-0219-z
PMCID: PMC4423399  PMID: 25940342
Recreational physical activity; Adherence; Theory of Planned Behaviour; Randomized control trial; Exercise intervention; Determinants
3.  Control Group Design, Contamination and Drop-Out in Exercise Oncology Trials: A Systematic Review 
PLoS ONE  2015;10(3):e0120996.
Purpose
Important considerations for exercise trials in cancer patients are contamination and differential drop-out among the control group members that might jeopardize the internal validity. This systematic review provides an overview of different control groups design characteristics of exercise-oncology trials and explores the association with contamination and drop-out rates.
Methods
Randomized controlled exercise-oncology trials from two Cochrane reviews were included. Additionally, a computer-aided search using Medline (Pubmed), Embase and CINAHL was conducted after completion date of the Cochrane reviews. Eligible studies were classified according to three control group design characteristics: the exercise instruction given to controls before start of the study (exercise allowed or not); and the intervention the control group was offered during (any (e.g., education sessions or telephone contacts) or none) or after (any (e.g., cross-over or exercise instruction) or none) the intervention period. Contamination (yes or no) and excess drop-out rates (i.e., drop-out rate of the control group minus the drop-out rate exercise group) were described according to the three design characteristics of the control group and according to the combinations of these three characteristics; so we additionally made subgroups based on combinations of type and timing of instructions received.
Results
40 exercise-oncology trials were included based on pre-specified eligibility criteria. The lowest contamination (7.1% of studies) and low drop-out rates (excess drop-out rate -4.7±9.2) were found in control groups offered an intervention after the intervention period. When control groups were offered an intervention both during and after the intervention period, contamination (0%) and excess drop-out rates (-10.0±12.8%) were even lower.
Conclusions
Control groups receiving an intervention during and after the study intervention period have lower contamination and drop-out rates. The present findings can be considered when designing future exercise-oncology trials.
doi:10.1371/journal.pone.0120996
PMCID: PMC4376879  PMID: 25815479
4.  African American breast cancer survivors’ preferences for various types of physical activity interventions: A Sisters Network Inc. web-based survey 
Background
Needs assessments are essential to developing lifestyle interventions for minority populations. To our knowledge, no physical activity (PA) needs assessment studies have been conducted for African American (AA) breast cancer survivors. The purpose of this study was to determine the PA intervention preferences of AA breast cancer survivors and determine whether these preferences differ according to medical and socio-demographic factors.
Methods
AA breast cancer survivors (N = 475, Mean age = 54 years) were recruited using ads sent via email and social media sites. Preferences for the mode of intervention delivery were assessed via web-based questionnaires. Descriptive statistics were used to characterize their interests in PA interventions, and subgroup differences were assessed.
Results
About 49% (142/291) of the participants who completed the survey were obese and 54% did not meet the recommended guidelines for PA. Most (90%) participants reported that they could participate in PA, and many (67%) indicated that they were interested in receiving program materials. Participants expressed the greatest interest in email (50%) or web-based (48%) programs over mail (45%), group (39%), and telephone (10%). Women also expressed the greatest interest in participating in studies that promoted walking and resistance or strength training. Intervention preferences did not differ significantly (P > 0.05) across socio-demographic or medical factors.
Conclusion
Most AA breast cancer survivors can participate in PA, and many are interested in interventions that promoted walking and resistance training and were delivered via the email or web. The development of culturally sensitive interventions that provide activities consistent with preferences can assist AA breast cancer survivors to adopt and maintain a healthy lifestyle.
Implications for cancer survivors
Despite evidence that AA breast cancer survivors are at increased risk for poor breast cancer-specific outcomes they are underrepresented in clinical trials promoting positive health behaviors. In this study, we propose to assess their exercise preferences and receptivity to a culturally appropriate physical activity intervention developed in collaboration with the Sisters Network. Health promotion programs developed in collaboration with a community based organization may aid in the development of research tools and resources that AA breast cancer survivors are receptive to using.
doi:10.1007/s11764-013-0307-5
PMCID: PMC4096148  PMID: 24043292
Breast cancer; African American women; cancer survivorship; cancer survivor; health disparities; physical activity
5.  Study design and methods for the Breast Cancer and Exercise Trial in Alberta (BETA) 
BMC Cancer  2014;14:919.
Background
Exercise has favorable effects on biomarkers associated with a lower risk of breast cancer, however it is unclear if higher doses of exercise provide additional effects. No clinical trial has systematically examined how different exercise volumes influence the mechanisms underlying breast cancer etiology. The Breast Cancer and Exercise Trial in Alberta (BETA) - a follow-up study to the Alberta Physical Activity and Breast Cancer Prevention (ALPHA) Trial - is examining how a one-year, high versus moderate volume aerobic exercise intervention influences several biomechanisms hypothesized to influence breast cancer risk in a group of postmenopausal women. Secondary aims are to compare intervention effects on psychosocial and quality of life outcomes as well as understand exercise adherence at 12 and 24 months, and maintenance of all study outcomes at 24 months.
Methods/Design
The BETA Trial is a two-center, two-armed randomized controlled exercise intervention trial conducted in 400 previously inactive, postmenopausal women aged 50–74 years, in Alberta, Canada. Participants were randomly assigned to a one-year aerobic exercise intervention of either high volume (300 minutes/week) or moderate volume (150 minutes/week). Blood draws and accelerometry were performed at baseline, six and 12 months. Baseline and 12-month measurements were taken of adiposity (including dual energy X-ray absorptiometry and computed tomography scans), physical fitness, dietary intake, self-reported physical activity and sedentary behavior, quality of life, perceived stress, happiness, sleep, and determinants of exercise adherence. Exercise maintenance was assessed and all study measurements were repeated at 24 months. Blood will be analyzed for endogenous estrogens, insulin resistance indicators, and inflammatory markers.
Discussion
The BETA Trial will compare the impact of a high versus moderate volume of aerobic exercise on a variety of biological, physiological, and psychological outcomes of relevance to postmenopausal women. A tightly controlled exercise intervention and objective outcome measurements are methodological strengths. The BETA Trial will inform future prevention initiatives by assessing adherence to a high volume of exercise over 12 months by postmenopausal women, and the ability of these women to maintain activity over the longer-term. The ultimate objective is to inform public health guidelines for reducing breast cancer risk through physical activity.
Trial registration
Clinical Trials Registration Number: NCT01435005
doi:10.1186/1471-2407-14-919
PMCID: PMC4364325  PMID: 25480020
Breast cancer; Physical activity; Adiposity; Estrogens; Insulin resistance; Inflammation; Quality of life
6.  A systematic review and meta-analysis of social cognitive theory-based physical activity and/or nutrition behavior change interventions for cancer survivors 
Journal of Cancer Survivorship  2014;9(2):305-338.
Purpose
Little is known about how to improve and create sustainable lifestyle behaviors of cancer survivors. Interventions based on social cognitive theory (SCT) have shown promise. This review examined the effect of SCT-based physical activity and nutrition interventions that target cancer survivors and identified factors associated with their efficacy.
Methods
A systematic search of seven databases identified randomized controlled trials that (i) targeted adult cancer survivors (any point from diagnosis); (ii) reported a primary outcome of physical activity, diet, or weight management; and (iii) included an SCT-based intervention targeting physical activity or diet. Qualitative synthesis and meta-analysis were conducted. Theoretical constructs and intervention characteristics were examined to identify factors associated with intervention efficacy.
Results
Eighteen studies (reported in 33 publications) met review inclusion criteria. Meta-analysis (n = 12) revealed a significant intervention effect for physical activity (standardized mean difference (SMD) = 0.33; P < 0.01). Most studies (six out of eight) that targeted dietary change reported significant improvements in at least one aspect of diet quality. No SCT constructs were associated with intervention effects. There were no consistent trends relating to intervention delivery method or whether the intervention targeted single or multiple behaviors.
Conclusions
SCT-based interventions demonstrate promise in improving physical activity and diet behavior in cancer survivors, using a range of intervention delivery modes. Further work is required to understand how and why these interventions offer promise for improving behavior.
Implications for Cancer Survivors
SCT-based interventions targeting diet or physical activity are safe and result in meaningful changes to diet and physical activity behavior that can result in health improvements.
doi:10.1007/s11764-014-0413-z
PMCID: PMC4441740  PMID: 25432633
Cancer; Physical activity; Nutrition; Systematic review; Social cognitive theory
7.  Type I and II Endometrial Cancers: Have They Different Risk Factors? 
Journal of Clinical Oncology  2013;31(20):2607-2618.
Purpose
Endometrial cancers have long been divided into estrogen-dependent type I and the less common clinically aggressive estrogen-independent type II. Little is known about risk factors for type II tumors because most studies lack sufficient cases to study these much less common tumors separately. We examined whether so-called classical endometrial cancer risk factors also influence the risk of type II tumors.
Patients and Methods
Individual-level data from 10 cohort and 14 case-control studies from the Epidemiology of Endometrial Cancer Consortium were pooled. A total of 14,069 endometrial cancer cases and 35,312 controls were included. We classified endometrioid (n = 7,246), adenocarcinoma not otherwise specified (n = 4,830), and adenocarcinoma with squamous differentiation (n = 777) as type I tumors and serous (n = 508) and mixed cell (n = 346) as type II tumors.
Results
Parity, oral contraceptive use, cigarette smoking, age at menarche, and diabetes were associated with type I and type II tumors to similar extents. Body mass index, however, had a greater effect on type I tumors than on type II tumors: odds ratio (OR) per 2 kg/m2 increase was 1.20 (95% CI, 1.19 to 1.21) for type I and 1.12 (95% CI, 1.09 to 1.14) for type II tumors (Pheterogeneity < .0001). Risk factor patterns for high-grade endometrioid tumors and type II tumors were similar.
Conclusion
The results of this pooled analysis suggest that the two endometrial cancer types share many common etiologic factors. The etiology of type II tumors may, therefore, not be completely estrogen independent, as previously believed.
doi:10.1200/JCO.2012.48.2596
PMCID: PMC3699726  PMID: 23733771
8.  Predictors of adherence to different types and doses of supervised exercise during breast cancer chemotherapy 
Background
Exercise is beneficial for breast cancer patients during chemotherapy but adherence to different types and doses of exercise is a challenge. The purpose of this study was to examine predictors of adherence to different types and doses of exercise during breast cancer chemotherapy in a multicenter randomized controlled trial.
Methods
Breast cancer patients in Edmonton, Vancouver, and Ottawa, Canada receiving chemotherapy (N = 301) were randomized to a standard dose of 25–30 minutes of aerobic exercise (STAN), a higher dose of 50–60 minutes of aerobic exercise (HIGH), or a higher dose of 50–60 minutes of combined aerobic and resistance exercise (COMB). Predictors included demographic, medical, fitness, and quality of life variables. Exercise adherence was measured as the percentage of supervised exercise sessions completed.
Results
Overall adherence to the supervised exercise sessions was 73% (SD = 24%). In a multivariate regression model, six independent predictors explained 26.4% (p < 0.001) of the variance in exercise adherence. Higher exercise adherence was achieved by breast cancer patients in Vancouver (p < 0.001), with fewer endocrine symptoms (p = 0.009), randomized to STAN (p = 0.009), with fewer exercise limitations (p = 0.009), receiving shorter chemotherapy protocols (p = 0.015), and with higher VO2peak (p = 0.017). Disease stage (p for interaction = 0.015) and body mass index (p for interaction = 0.030) interacted with group assignment to predict adherence. For disease stage, patients with stage I/IIa disease adhered equally well to all three exercise interventions whereas patients with stage IIb/III disease adhered better to the STAN intervention than the two higher dose exercise interventions. For body mass index, healthy weight patients adhered equally well to all three exercise interventions whereas overweight patients adhered best to STAN and worst to COMB; and obese patients adhered best to STAN and worst to HIGH.
Conclusions
Determinants of exercise adherence in breast cancer patients receiving chemotherapy are multidisciplinary and may vary by the exercise prescription.
doi:10.1186/s12966-014-0085-0
PMCID: PMC4110703  PMID: 24997476
Adherence; Cancer treatment; Cancer survivors; Determinants; Physical activity
9.  Effects of a physical activity behavior change intervention on inflammation and related health outcomes in breast cancer survivors: pilot randomized trial 
Integrative cancer therapies  2012;12(4):323-335.
Background
Physical activity may provide benefits for breast cancer survivors in part by reducing systemic inflammation. Physical activity behavior change studies are a type of implementation research in which exercise efficacy information is translated into a “real world” setting, allowing determination of whether physical activity changes are sufficient to improve health outcomes. We hypothesized that breast cancer survivors (BCS) who undertook a physical activity behavior change intervention would have less systemic inflammation and improved cardiorespiratory fitness, muscle strength, body composition, fatigue, and sleep as compared with BCS receiving usual care. The goal of this pilot study was to determine the magnitude and direction of intervention effect sizes for inflammatory related serum markers and relevant health outcomes.
Methods
This randomized controlled trial enrolled 28 Stage I, II, or IIIA BCS who were post-primary treatment and were not regular exercisers. These women were assigned to either a 3-month physical activity behavior change intervention group (ING) or usual care group (UCG). Intervention included supervised aerobic (150 weekly minutes, moderate-intensity) and resistance (two sessions per week) exercise that gradually tapered to home-based exercise. At baseline and after 3 months, health outcomes and serum concentrations of interleukin (IL)-1 beta, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-alpha, leptin, and adiponectin were measured.
Results
Cardiorespiratory fitness significantly improved in the ING versus UCG (between group difference=3.8 ml/kg/min; d=1.1; P=0.015). Self-reported sleep latency was significantly reduced in the ING versus UCG (between group difference=−0.5; d=−1.2; P=0.02) as was serum leptin (between group difference=−9.0 ng/ml; d=−1.0; P=0.031). Small to medium non-significant negative effect sizes were noted for IL-10 and TNF-alpha and ratios of IL-6:IL-10, IL-8:IL10, and TNF-alpha:IL-10, with non-significant positive effect sizes noted for IL-6 and high molecular weight adiponectin.
Conclusions
Physical activity behavior change interventions in BCS can achieve large effect size changes for several health outcomes. Although effect sizes for inflammatory markers were often small and not significant, changes were in the hypothesized direction for all except IL-6 and IL-10. These preliminary data support larger trials that would more fully examine potential inflammatory changes that accompany physical activity behavior change interventions.
doi:10.1177/1534735412449687
PMCID: PMC3909487  PMID: 22831916
exercise; intervention; oncology; cytokine; inflammation; survivorship
10.  Anthropometric Measures and the Risk of Endometrial Cancer, Overall and by Tumor Microsatellite Status and Histological Subtype 
American Journal of Epidemiology  2013;177(12):1378-1387.
Obesity is an established risk factor for endometrial cancer, but this association is not well understood for subtypes of endometrial cancer. We evaluated the association of recent and adult-life obesity with subtypes of endometrial cancer based on microsatellite status (microsatellite-stable (MSS) vs. microsatellite-instable (MSI)) and histology (type I vs. type II). Analyses were based on a population-based case-control study (524 cases and 1,032 controls) conducted in Alberta, Canada (2002–2006) and included the following groupings of subtypes: MSS = 337 and MSI = 130; type I = 458 and type II = 66. Logistic and polytomous logistic regression were used to estimate odds ratios and 95% confidence intervals for overall endometrial cancer and subtypes of endometrial cancer, respectively. The risks of all subtypes of endometrial cancer, except type II, increased with an increase in all of the anthropometric characteristics examined. The risks for MSI tumors were suggestively stronger than those for MSS tumors; the risk with high (≥30) body mass index (weight (kg)/height (m)2) was significantly stronger for MSI tumors (odds ratio = 4.96, 95% confidence interval: 2.76, 8.91) than for MSS tumors (odds ratio = 2.33, 95% confidence interval: 1.66, 3.28) (P-heterogeneity = 0.02). Obesity is associated with most subtypes of endometrial cancer, and further studies are warranted to elucidate the biological mechanisms underlying the stronger risk for the MSI subtype with a high body mass index.
doi:10.1093/aje/kws434
PMCID: PMC3732018  PMID: 23673247
DNA mismatch repair; endometrial neoplasms; microsatellite instability; risk factors
11.  Randomized controlled trial to evaluate the effects of combined progressive exercise on metabolic syndrome in breast cancer survivors: rationale, design, and methods 
BMC Cancer  2014;14:238.
Background
Metabolic syndrome (MetS) is increasingly present in breast cancer survivors, possibly worsened by cancer-related treatments, such as chemotherapy. MetS greatly increases risk of cardiovascular disease and diabetes, co-morbidities that could impair the survivorship experience, and possibly lead to cancer recurrence. Exercise has been shown to positively influence quality of life (QOL), physical function, muscular strength and endurance, reduce fatigue, and improve emotional well-being; however, the impact on MetS components (visceral adiposity, hyperglycemia, low serum high-density lipoprotein cholesterol, hypertriglyceridemia, and hypertension) remains largely unknown. In this trial, we aim to assess the effects of combined (aerobic and resistance) exercise on components of MetS, as well as on physical fitness and QOL, in breast cancer survivors soon after completing cancer-related treatments.
Methods/Design
This study is a prospective randomized controlled trial (RCT) investigating the effects of a 16-week supervised progressive aerobic and resistance exercise training intervention on MetS in 100 breast cancer survivors. Main inclusion criteria are histologically-confirmed breast cancer stage I-III, completion of chemotherapy and/or radiation within 6 months prior to initiation of the study, sedentary, and free from musculoskeletal disorders. The primary endpoint is MetS; secondary endpoints include: muscle strength, shoulder function, cardiorespiratory fitness, body composition, bone mineral density, and QOL. Participants randomized to the Exercise group participate in 3 supervised weekly exercise sessions for 16 weeks. Participants randomized to the Control group are offered the same intervention after the 16-week period of observation.
Discussion
This is the one of few RCTs examining the effects of exercise on MetS in breast cancer survivors. Results will contribute a better understanding of metabolic disease-related effects of resistance and aerobic exercise training and inform intervention programs that will optimally improve physiological and psychosocial health during cancer survivorship, and that are ultimately aimed at improving prognosis.
Trial registration
NCT01140282; Registration: June 10, 2010
doi:10.1186/1471-2407-14-238
PMCID: PMC3985576  PMID: 24708832
Exercise; Breast cancer; Metabolic syndrome
12.  Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS): rationale and design for meta-analyses of individual patient data of randomized controlled trials that evaluate the effect of physical activity and psychosocial interventions on health-related quality of life in cancer survivors 
Systematic Reviews  2013;2:75.
Background
Effective interventions to improve quality of life of cancer survivors are essential. Numerous randomized controlled trials have evaluated the effects of physical activity or psychosocial interventions on health-related quality of life of cancer survivors, with generally small sample sizes and modest effects. Better targeted interventions may result in larger effects. To realize such targeted interventions, we must determine which interventions that are presently available work for which patients, and what the underlying mechanisms are (that is, the moderators and mediators of physical activity and psychosocial interventions). Individual patient data meta-analysis has been described as the ‘gold standard’ of systematic review methodology. Instead of extracting aggregate data from study reports or from authors, the original research data are sought directly from the investigators. Individual patient data meta-analyses allow for adequate statistical analysis of intervention effects and moderators of such effects.
Here, we report the rationale and design of the Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS) Consortium. The primary aim of POLARIS is 1) to conduct meta-analyses based on individual patient data to evaluate the effect of physical activity and psychosocial interventions on the health-related quality of life of cancer survivors; 2) to identify important demographic, clinical, personal, or intervention-related moderators of the effect; and 3) to build and validate clinical prediction models identifying the most relevant predictors of intervention success.
Methods/Design
We will invite investigators of randomized controlled trials that evaluate the effects of physical activity and/or psychosocial interventions on health-related quality of life compared with a wait-list, usual care or attention control group among adult cancer survivors to join the POLARIS consortium and share their data for use in pooled analyses that will address the proposed aims. We are in the process of identifying eligible randomized controlled trials through literature searches in four databases. To date, we have identified 132 eligible and unique trials.
Discussion
The POLARIS consortium will conduct the first individual patient data meta-analyses in order to generate evidence essential to targeting physical activity and psychosocial programs to the individual survivor’s characteristics, capabilities, and preferences.
Registration
PROSPERO: International prospective register of systematic reviews, CRD42013003805
doi:10.1186/2046-4053-2-75
PMCID: PMC3848838  PMID: 24034173
Physical activity; Exercise; Neoplasms; Psychotherapy; Health-related quality of life; Rehabilitation; Individual patient data meta-analysis
13.  Associations among physical activity, body mass index, and health-related quality of life by race/ethnicity in a diverse sample of breast cancer survivors 
Cancer  2012;118(16):4024-4031.
Background
Health-related quality of life (HRQOL), body mass index (BMI), and physical activity (PA) levels have all been associated with prognosis following breast cancer and may partially explain higher mortality for breast cancer in certain race/ethnic sub-groups. In this study, we examined associations between PA, BMI, and HRQOL by race in a sample of breast cancer survivors.
Methods
Measures of PA, BMI, and HRQOL as well as demographic and medical characteristics of women (N=3013, 13% nonwhite) who participated in the Women’s Healthy Eating and Living Study were assessed at baseline. Analysis of covariance was used to examine the relationship between PA and obesity with HRQOL outcomes. Statistical tests were two-sided.
Results
African-American women were less likely to meet guidelines for PA and more likely to be obese than women from other ethnic groups (P < 0.05). In adjusted models, women who met guidelines for PA reported significantly higher physical health composite (point differences ranged from 10.5 to 21.2 points, all P <0.05) and vitality (point differences ranged from 9.9 to 16.5 points, all P <0.05) scores than those who did not, regardless of race/ethnicity. Associations between obesity and HRQOL were mixed with fewer associations for Asian-American and African-American women and stronger associations for whites.
Conclusion
Breast cancer survivors from racially and ethnically diverse populations have lower levels of PA and higher rates of obesity that are generally associated with poorer HRQOL. Culturally sensitive PA and weight loss interventions may improve these lifestyle characteristics and result in improved HRQOL.
doi:10.1002/cncr.27389
PMCID: PMC3330155  PMID: 22252966
breast neoplasm; African American; disparities; Hispanic; obesity; quality of life; cancer survivors
14.  Case–control study of lifetime alcohol consumption and endometrial cancer risk 
Cancer Causes & Control  2013;24(11):1995-2003.
Purpose
Alcohol consumption is hypothesized to increase the risk of endometrial cancer by increasing circulating estrogen levels. This study sought to investigate the association between lifetime alcohol consumption and endometrial cancer risk.
Methods
We recruited 514 incident endometrial cancer cases and 962 frequency age-matched controls in this population-based case–control study in Alberta, Canada, from 2002 to 2006. Participants completed in-person interviews querying lifetime alcohol consumption and other relevant health and lifestyle factors. Participants reported the usual number of drinks of beer, wine, and liquor consumed; this information was compiled for each drinking pattern reported over the lifetime to estimate average lifetime exposure to alcohol.
Results
Lifetime average alcohol consumption was relatively low (median intake: 3.9 g/day for cases, 4.9 g/day for controls). Compared with lifetime abstainers, women consuming >2.68 and ≤8.04 g/day alcohol and >8.04 g/day alcohol on average over the lifetime showed 38 and 35 % lower risks of endometrial cancer, respectively (p trend = 0.023). In addition, average lifetime consumption of all types of alcohol was associated with decreased risks. There was no evidence for effect modification by body mass index, physical activity, menopausal status, and hormone replacement therapy use combined and effects did not differ by type of endometrial cancer (type I or II).
Conclusion
This study provides epidemiologic evidence for an inverse association between relatively modest lifetime average alcohol consumption (approximately 1/4 to 1/2 drink/day) and endometrial cancer risk. The direction of this relation is consistent with previous studies that examined similar levels of alcohol intake.
doi:10.1007/s10552-013-0275-0
PMCID: PMC3824213  PMID: 23929278
Endometrial cancer; Alcohol drinking; Ethanol; Beer; Wine; Liquor
15.  The Role of Obesity in Cancer Survival and Recurrence 
Obesity and components of energy imbalance, i.e., excessive energy intake and suboptimal levels of physical activity, are established risk factors for cancer incidence. Accumulating evidence suggests that these factors also may be important after the diagnosis of cancer and influence the course of disease, as well as overall health, well-being, and survival. Lifestyle and medical interventions that effectively modify these factors could potentially be harnessed as a means of cancer control. However, for such interventions to be maximally effective and sustainable, broad sweeping scientific discoveries ranging from molecular and cellular advances, to developments in delivering interventions on both individual and societal levels are needed. This review summarizes key discussion topics that were addressed in a recent Institute of Medicine Workshop entitled, “The Role of Obesity in Cancer Survival and Recurrence”; discussions included: 1) mechanisms associated with obesity and energy balance that influence cancer progression; 2) complexities of studying and interpreting energy balance in relation to cancer recurrence and survival; 3) associations between obesity and cancer risk, recurrence, and mortality; 4) interventions that promote weight loss, increased physical activity, and negative energy balance as a means of cancer control; and 5) future directions.
doi:10.1158/1055-9965.EPI-12-0485
PMCID: PMC3415558  PMID: 22695735
neoplasms; obesity; diet; physical activity; survival; recurrence
16.  Cardiopulmonary Function and Age-Related Decline Across the Breast Cancer Survivorship Continuum 
Journal of Clinical Oncology  2012;30(20):2530-2537.
Purpose
To evaluate cardiopulmonary function (as measured by peak oxygen consumption [VO2peak]) across the breast cancer continuum and its prognostic significance in women with metastatic disease.
Patients and Methods
Patients with breast cancer representing four cross-sectional cohorts—that is, (1) before, (2) during, and (3) after adjuvant therapy for nonmetastatic disease, and (4) during therapy in metastatic disease—were studied. A cardiopulmonary exercise test (CPET) with expired gas analysis was used to assess VO2peak. A Cox proportional hazards model was used to estimate the risk of death according to VO2peak category (< 15.4 v ≥ 15.4 mL · kg−1 · min−1) with adjustment for clinical factors.
Results
A total of 248 women (age, 55 ± 8 years) completed a CPET. Mean VO2peak was 17.8 ± a standard deviation of 4.3 mL · kg−1 · min−1, the equivalent of 27% ± 17% below age-matched healthy sedentary women. For the entire cohort, 32% had a VO2peak less than 15.4 mL · kg−1 · min−1—the VO2peak required for functional independence. VO2peak was significantly different across breast cancer cohorts for relative (mL · kg−1 · min−1) and absolute (L · min−1) VO2peak (P = .017 and P < .001, respectively); VO2peak was lowest in women with metastatic disease. In patients with metastatic disease (n = 52), compared with patients achieving a VO2peak ≤ 1.09 L · min−1, the adjusted hazard ratio for death was 0.32 (95% CI, 0.16 to 0.67, P = .002) for a VO2peak more than 1.09 L · min−1.
Conclusion
Patients with breast cancer have marked impairment in VO2peak across the entire survivorship continuum. VO2peak may be an independent predictor of survival in metastatic disease.
doi:10.1200/JCO.2011.39.9014
PMCID: PMC3397786  PMID: 22614980
17.  Perceived benefits and barriers to exercise for recently treated patients with multiple myeloma: a qualitative study 
BMC Cancer  2013;13:319.
Background
Understanding the physical activity experiences of patients with multiple myeloma (MM) is essential to inform the development of evidence-based interventions and to quantify the benefits of physical activity. The aim of this study was to gain an in-depth understanding of the physical activity experiences and perceived benefits and barriers to physical activity for patients with MM.
Methods
This was a qualitative study that used a grounded theory approach. Semi-structured interviews were conducted in Victoria, Australia by telephone from December 2011-February 2012 with patients who had been treated for MM within the preceding 2–12 months. Interviews were transcribed and analysed using the constant comparison coding method to reduce the data to themes. Gender differences and differences between treatment groups were explored.
Results
Twenty-four interviews were completed. The sample comprised 13 females (54%), with a mean age of 62 years (SD = 8.8). Sixteen (67%) participants had received an autologous stem cell transplant (ASCT). All participants currently engaged in a range of light to moderate intensity physical activity; walking and gardening were the most common activities. Recovery from the symptoms of MM and side effects of therapy, psychological benefits, social factors and enjoyment were important benefits of physical activity. Barriers to physical activity predominately related to the symptoms of MM and side effects of therapy, including pain, fatigue, and fear of infection. Low self- motivation was also a barrier. Women participated in a more diverse range of physical activities than men and there were gender differences in preferred type of physical activity. Women were more likely to report psychological and social benefits; whereas men reported physical activity as a way to keep busy and self-motivation was a barrier. Patients treated with an ASCT more often reported affective benefits of participation in physical activity and fatigue as a barrier. Patients treated with other therapies (e.g., chemotherapy, radiotherapy) were more likely to report pain as a barrier.
Conclusions
Patients with MM experience debilitating effects of their condition and therapy, which influences their level and intensity of physical activity participation. Physical activity programs should be individualised; take into consideration gender differences and the impact of different types of therapy on physical activity; and focus on meeting the psychological, coping and recovery needs of patients.
doi:10.1186/1471-2407-13-319
PMCID: PMC3702408  PMID: 23815855
Cancer; Oncology; Multiple Myeloma; Physical Activity; Exercise
18.  Physical Activity, Biomarkers, and Disease Outcomes in Cancer Survivors: A Systematic Review 
Background
Cancer survivors often seek information about how lifestyle factors, such as physical activity, may influence their prognosis. We systematically reviewed studies that examined relationships between physical activity and mortality (cancer-specific and all-cause) and/or cancer biomarkers.
Methods
We identified 45 articles published from January 1950 to August 2011 through MEDLINE database searches that were related to physical activity, cancer survival, and biomarkers potentially relevant to cancer survival. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement to guide this review. Study characteristics, mortality outcomes, and biomarker-relevant and subgroup results were abstracted for each article that met the inclusion criteria (ie, research articles that included participants with a cancer diagnosis, mortality outcomes, and an assessment of physical activity).
Results
There was consistent evidence from 27 observational studies that physical activity is associated with reduced all-cause, breast cancer–specific, and colon cancer–specific mortality. There is currently insufficient evidence regarding the association between physical activity and mortality for survivors of other cancers. Randomized controlled trials of exercise that included biomarker endpoints suggest that exercise may result in beneficial changes in the circulating level of insulin, insulin-related pathways, inflammation, and, possibly, immunity; however, the evidence is still preliminary.
Conclusions
Future research directions identified include the need for more observational studies on additional types of cancer with larger sample sizes; the need to examine whether the association between physical activity and mortality varies by tumor, clinical, or risk factor characteristics; and the need for research on the biological mechanisms involved in the association between physical activity and survival after a cancer diagnosis. Future randomized controlled trials of exercise with biomarker and cancer-specific disease endpoints, such as recurrence, new primary cancers, and cancer-specific mortality in cancer survivors, are warranted.
doi:10.1093/jnci/djs207
PMCID: PMC3465697  PMID: 22570317
19.  Home-based functional walking program for advanced cancer patients receiving palliative care: a case series 
BMC Palliative Care  2013;12:22.
Background
Although meta-analyses have demonstrated that physical activity can positively impact quality of life outcomes in early stage cancer patients, it is not yet known whether these benefits can be extended to patients with advanced cancer. In a previous pilot survey of patients with advanced cancer with a median survival of 104 days, participants felt willing and able to participate in a physical activity intervention, and reported a strong preference for walking and home-based programming. Here, we report on the initial development and feasibility of a home-based functional walking program in patients with advanced cancer receiving palliative care.
Methods
Nine adult patients were recruited from outpatient palliative care clinics and palliative home care. A pilot intervention trial was conducted over a 6-week period. The McGill Quality of Life Questionnaire (MQOL), Late Life Function and Disability Instrument (LLFDI), Edmonton Symptom Assessment System (ESAS), Seniors Fitness Test, four-test balance scale, and grip strength, were performed pre- and post-intervention. Participants wore activPAL™ accelerometers to monitor ambulatory activity levels.
Results
Of the nine recruited participants, three participants dropped out prior to baseline testing due to hospital admission and feeling overwhelmed, and three participants dropped out during the intervention due to severe symptoms. Only three participants completed the intervention program, pre- and post-intervention assessments: two reported improvements in total MQOL scores, yet all three shared an overall trend towards worsening symptom and total fatigue scores post-intervention. Two participants passed away within 90 days of completing the intervention.
Conclusions
This case series demonstrates the challenges of a physical activity intervention in patients with advanced cancer receiving palliative care. Further feasibility research is required in this patient population.
Trial registration
This study is registered under ClinicalTrials.gov as NCT00438620.
doi:10.1186/1472-684X-12-22
PMCID: PMC3655875  PMID: 23663868
Physical activity; Palliative care; Cancer; Quality of life; Walking
20.  Lifestyle Behaviors of African American Breast Cancer Survivors: A Sisters Network, Inc. Study 
PLoS ONE  2013;8(4):e61854.
Introduction
African American breast cancer survivors experience poor cancer outcomes that may, in part, be remedied by healthy lifestyle choices. Few studies have evaluated the health and lifestyle behaviors of this population. The purpose of this study was to characterize the health and lifestyle habits of African American breast cancer survivors and evaluate the socio-demographic and medical correlates of these behaviors.
Methods
A total of 470 African American breast cancer survivors (mean age = 54 years) participated in an online survey. All participants completed measures assessing medical and demographic characteristics, physical activity, and sedentary behavior. Chi-square tests for association, nonparametric tests, and logistic regression models were used to assess associations. All statistical tests were two sided.
Results
Almost half (47%) of the women met the current guidelines for physical activity, almost half (47%) were obese, and many reported having high blood pressure (53%) or diabetes (21%). The prevalence of high blood pressure, diabetes, and high cholesterol increased by age (P<0.001), and obese women had a higher prevalence of high blood pressure (63% vs. 44%) and diabetes (21% vs. 12%) than did non-obese women (all P<0.05). Obese women participated in significantly fewer total minutes of physical activity per week (100 minutes/week) than did non-obese women (150 minutes/week; P<0.05). The number of comorbid conditions was associated with increased odds for physical inactivity (odds ratio = 1.40) and obesity (odds ratio = 2.22).
Conclusion
Many African American breast cancer survivors had chronic conditions that may be exacerbated by poor lifestyle choices. Our results also provide evidence that healthy lifestyle interventions among obese African American breast cancer survivors are urgently needed.
doi:10.1371/journal.pone.0061854
PMCID: PMC3633932  PMID: 23626740
21.  Implementing the Exercise Guidelines for Cancer Survivors 
In 2009, the American College of Sports Medicine convened an expert roundtable to issue guidelines on exercise for cancer survivors. This multidisciplinary group evaluated the strength of the evidence for the safety and benefits of exercise as a therapeutic intervention for survivors. The panel concluded that exercise is safe and offers myriad benefits for survivors including improvements in physical function, strength, fatigue, quality of life (QOL), and possibly recurrence and survival. Recommendations for situations in which deviations from the US Physical Activity Guidelines for Americans are appropriate were provided. Here, we outline a process for implementing the guidelines in clinical practice, and provide recommendations for how the oncology care provider can interface with the exercise and physical therapy community.
doi:10.1016/j.suponc.2012.02.001
PMCID: PMC3543866  PMID: 22579268
exercise; physical therapy; survivorship; cancer; rehabilitation; health promotion
22.  Better exercise adherence after treatment for cancer (BEAT Cancer) study: Rationale, design, and methods 
Contemporary Clinical Trials  2011;33(1):124-137.
Most breast cancer survivors do not engage in regular physical activity. Our physical activity behavior change intervention for breast cancer survivors significantly improved physical activity and health outcomes post-intervention during a pilot, feasibility study. Testing in additional sites with a larger sample and longer follow-up is warranted to confirm program effectiveness short and longer term. Importantly, the pilot intervention resulted in changes in physical activity and social cognitive theory constructs, enhancing our potential for testing mechanisms mediating physical activity behavior change. Here, we report the rationale, design, and methods for a two-site, randomized controlled trial comparing the effects of the BEAT Cancer physical activity behavior change intervention to usual care on short and longer term physical activity adherence among breast cancer survivors. Secondary aims include examining social cognitive theory mechanisms of physical activity behavior change and health benefits of the intervention. Study recruitment goal is 256 breast cancer survivors with a history of ductal carcinoma in situ or Stage I, II, or IIIA disease who have completed primary cancer treatment. Outcome measures are obtained at baseline, 3 months (i.e., immediately post-intervention), 6 months, and 12 months and include physical activity, psychosocial factors, fatigue, sleep quality, lower extremity joint dysfunction, cardiorespiratory fitness, muscle strength, and waist-to-hip ratio. Confirming behavior change effectiveness, health effects, and underlying mechanisms of physical activity behavior change interventions will facilitate translation to community settings for improving the health and well-being of breast cancer survivors.
doi:10.1016/j.cct.2011.09.004
PMCID: PMC3253876  PMID: 21983625
oncology; exercise; survivorship; predictors; adherence
23.  Exercise Effects on Depressive Symptoms in Cancer Survivors: A Systematic Review and Meta-Analysis 
Background
Depression is a distressing side effect of cancer and its treatment. In the general population, exercise is an effective antidepressant.
Objective
We conducted a systematic review and meta-analysis to determine the antidepressant effect of exercise in cancer survivors.
Data Sources
In May, 2011, we searched MEDLINE, PsycInfo, EMBASE, CINAHL, CDSR, CENTRAL, AMED, Biosis Previews, and Sport Discus, and citations from relevant papers and reviews.
Study Eligibility Criteria
We included randomized controlled trials (RCTs) comparing exercise interventions to usual care in cancer survivors, utilizing a self-report inventory or clinician rating to assess depressive symptoms, and reporting symptoms pre- and post-intervention.
Study Appraisal
7,042 study titles were identified and screened, with 15 RCTs included.
Synthesis Methods
Effect sizes (ES) were reported as mean change scores. The Q test was conducted to evaluate heterogeneity of ES. Potential moderator variables were evaluated with examination of scatter plots and Wilcoxon rank-sum or Kruskal-Wallis tests.
Results
The overall ES, under a random effects model, was −0.22 (CI −0.43, −0.09, p = 0.04). Significant moderating variables (ps < .05) were exercise location, exercise supervision, and exercise duration.
Limitations
Only one study identified depression as the primary endpoint.
Conclusions
Exercise has modest positive effects on depressive symptoms with larger effects for programs that were supervised or partially supervised, not performed at home, and at least 30 minutes in duration.
Impact
Our results complement other studies showing that exercise is associated with reduced pain and fatigue and with improvements in quality of life among cancer survivors.
doi:10.1158/1055-9965.EPI-11-0634
PMCID: PMC3253916  PMID: 22068286
physical activity; mental health; cancer survivorship
24.  Case–control study of markers of insulin resistance and endometrial cancer risk 
Endocrine-Related Cancer  2012;19(6):785-792.
Markers of insulin resistance such as the adiponectin:leptin ratio (A:L) and the homeostasis model assessment ratio (HOMA-IR) are associated with obesity and hyperinsulinemia, both established risk factors for endometrial cancer, and may therefore be informative regarding endometrial cancer risk. This study investigated the association between endometrial cancer risk and markers of insulin resistance, namely adiponectin, leptin, the A:L ratio, insulin, fasting glucose, and the HOMA-IR. We analyzed data from 541 incident endometrial cancer cases and 961 frequency age-matched controls in a population-based case–control study in Alberta, Canada from 2002 to 2006. Participants completed interview-administered questionnaires were assessed for anthropometric measures, and provided 8-h fasting blood samples either pre- or postoperatively. Blood was analyzed for concentrations of leptin, adiponectin, and insulin by immunoassay, and fasting plasma glucose levels were determined by fluorimetric quantitative determination. Compared with the lowest quartile, the highest quartile of insulin and HOMA-IR was associated with 64% (95% confidence intervals (CI): 1.12–2.40) and 72% (95% CI: 1.17–2.53) increased risks of endometrial cancer, respectively, and the highest quartile of adiponectin was associated with a 45% (95% CI: 0.37–0.80) decreased risk after multivariable adjustments. Null associations were observed between fasting glucose, leptin and A:L, and endometrial cancer risk. This population-based study provides evidence for a role of insulin resistance in endometrial cancer etiology and may provide one possible pathway whereby obesity increases the risk of this common cancer. Interventions aimed at decreasing both obesity and insulin resistance may decrease endometrial cancer risk.
doi:10.1530/ERC-12-0211
PMCID: PMC3493985  PMID: 23033315
25.  The Alberta moving beyond breast cancer (AMBER) cohort study: a prospective study of physical activity and health-related fitness in breast cancer survivors 
BMC Cancer  2012;12:525.
Background
Limited research has examined the association between physical activity, health-related fitness, and disease outcomes in breast cancer survivors. Here, we present the rationale and design of the Alberta Moving Beyond Breast Cancer (AMBER) Study, a prospective cohort study designed specifically to examine the role of physical activity and health-related fitness in breast cancer survivorship from the time of diagnosis and for the balance of life. The AMBER Study will examine the role of physical activity and health-related fitness in facilitating treatment completion, alleviating treatment side effects, hastening recovery after treatments, improving long term quality of life, and reducing the risks of disease recurrence, other chronic diseases, and premature death.
Methods/Design
The AMBER Study will enroll 1500 newly diagnosed, incident, stage I-IIIc breast cancer survivors in Alberta, Canada over a 5 year period. Assessments will be made at baseline (within 90 days of surgery), 1 year, and 3 years consisting of objective and self-reported measurements of physical activity, health-related fitness, blood collection, lymphedema, patient-reported outcomes, and determinants of physical activity. A final assessment at 5 years will measure patient-reported data only. The cohort members will be followed for an additional 5 years for disease outcomes.
Discussion
The AMBER cohort will answer key questions related to physical activity and health-related fitness in breast cancer survivors including: (1) the independent and interactive associations of physical activity and health-related fitness with disease outcomes (e.g., recurrence, breast cancer-specific mortality, overall survival), treatment completion rates, symptoms and side effects (e.g., pain, lymphedema, fatigue, neuropathy), quality of life, and psychosocial functioning (e.g., anxiety, depression, self-esteem, happiness), (2) the determinants of physical activity and health-related fitness including demographic, medical, social cognitive, and environmental variables, (3) the mediators of any observed associations between physical activity, health-related fitness, and health outcomes including biological, functional, and psychosocial, and (4) the moderators of any observed associations including demographic, medical, and biological/disease factors. Taken together, these data will provide a comprehensive inquiry into the outcomes, determinants, mechanisms, and moderators of physical activity and health-related fitness in breast cancer survivors.
doi:10.1186/1471-2407-12-525
PMCID: PMC3534483  PMID: 23153358
Breast cancer; Exercise; Physical activity; Cardiorespiratory fitness; Muscular strength; Lymphedema; Quality of life; Exercise determinants; Recurrence; Survival

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