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1.  Type I and II Endometrial Cancers: Have They Different Risk Factors? 
Journal of Clinical Oncology  2013;31(20):2607-2618.
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.
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.
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.
PMCID: PMC3699726  PMID: 23733771
2.  Predictors of adherence to different types and doses of supervised exercise during breast cancer chemotherapy 
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.
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.
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.
Determinants of exercise adherence in breast cancer patients receiving chemotherapy are multidisciplinary and may vary by the exercise prescription.
PMCID: PMC4110703  PMID: 24997476
Adherence; Cancer treatment; Cancer survivors; Determinants; Physical activity
3.  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.
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.
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.
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.
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.
PMCID: PMC3909487  PMID: 22831916
exercise; intervention; oncology; cytokine; inflammation; survivorship
4.  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.
PMCID: PMC3732018  PMID: 23673247
DNA mismatch repair; endometrial neoplasms; microsatellite instability; risk factors
5.  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.
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.
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.
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
PMCID: PMC3985576  PMID: 24708832
Exercise; Breast cancer; Metabolic syndrome
6.  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.
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.
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.
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.
PROSPERO: International prospective register of systematic reviews, CRD42013003805
PMCID: PMC3848838  PMID: 24034173
Physical activity; Exercise; Neoplasms; Psychotherapy; Health-related quality of life; Rehabilitation; Individual patient data meta-analysis
7.  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.
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.
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.
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.
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.
PMCID: PMC3330155  PMID: 22252966
breast neoplasm; African American; disparities; Hispanic; obesity; quality of life; cancer survivors
8.  Case–control study of lifetime alcohol consumption and endometrial cancer risk 
Cancer Causes & Control  2013;24(11):1995-2003.
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.
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.
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).
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.
PMCID: PMC3824213  PMID: 23929278
Endometrial cancer; Alcohol drinking; Ethanol; Beer; Wine; Liquor
9.  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.
PMCID: PMC3415558  PMID: 22695735
neoplasms; obesity; diet; physical activity; survival; recurrence
10.  Cardiopulmonary Function and Age-Related Decline Across the Breast Cancer Survivorship Continuum 
Journal of Clinical Oncology  2012;30(20):2530-2537.
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.
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.
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.
PMCID: PMC3397786  PMID: 22614980
11.  Perceived benefits and barriers to exercise for recently treated patients with multiple myeloma: a qualitative study 
BMC Cancer  2013;13:319.
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.
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.
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.
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.
PMCID: PMC3702408  PMID: 23815855
Cancer; Oncology; Multiple Myeloma; Physical Activity; Exercise
12.  Physical Activity, Biomarkers, and Disease Outcomes in Cancer Survivors: A Systematic Review 
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.
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).
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.
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.
PMCID: PMC3465697  PMID: 22570317
13.  Home-based functional walking program for advanced cancer patients receiving palliative care: a case series 
BMC Palliative Care  2013;12:22.
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.
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.
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.
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 as NCT00438620.
PMCID: PMC3655875  PMID: 23663868
Physical activity; Palliative care; Cancer; Quality of life; Walking
14.  Lifestyle Behaviors of African American Breast Cancer Survivors: A Sisters Network, Inc. Study 
PLoS ONE  2013;8(4):e61854.
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.
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.
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).
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.
PMCID: PMC3633932  PMID: 23626740
15.  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.
PMCID: PMC3543866  PMID: 22579268
exercise; physical therapy; survivorship; cancer; rehabilitation; health promotion
16.  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.
PMCID: PMC3253876  PMID: 21983625
oncology; exercise; survivorship; predictors; adherence
17.  Exercise Effects on Depressive Symptoms in Cancer Survivors: A Systematic Review and Meta-Analysis 
Depression is a distressing side effect of cancer and its treatment. In the general population, exercise is an effective antidepressant.
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.
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.
Only one study identified depression as the primary endpoint.
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.
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.
PMCID: PMC3253916  PMID: 22068286
physical activity; mental health; cancer survivorship
18.  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.
PMCID: PMC3493985  PMID: 23033315
19.  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.
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.
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.
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.
PMCID: PMC3534483  PMID: 23153358
Breast cancer; Exercise; Physical activity; Cardiorespiratory fitness; Muscular strength; Lymphedema; Quality of life; Exercise determinants; Recurrence; Survival
20.  Correlates of physical activity in a population-based sample of kidney cancer survivors: an application of the theory of planned behavior 
Over half of kidney cancer survivors (KCS) are completely inactive and only a quarter are meeting physical activity (PA) guidelines. This highlights the need to identify and understand the determinants of PA in this understudied population. The purpose of this study is to determine the social cognitive correlates of PA intention and behavior in KCS using the Theory of Planned Behavior (TPB).
All 1,985 KCS diagnosed between 1996 and 2010 in Alberta, Canada were mailed a self-report survey that consisted of the Godin Leisure Time Exercise Questionnaire and standard TPB items for intention, planning, perceived behavioral control (PBC), affective and instrumental attitudes, and descriptive and injunctive norms. Standard demographic and medical variables were also collected.
Completed surveys were received from 703 of 1,654 (43%) eligible KCS. The TPB was tested using structural equation modelling and demonstrated an adequate-to-good fit to the data [χ² = 256.88, p < .001; TLI = 0.97; CFI = 0.98; RMSEA = 0.06, 90% CI = 0.05-0.06].
There were significant pathways to PA from PBC (ß = 0.18, p = 0.02), planning (ß = 0.22, p < 0.01), and intention (ß = 0.31, p < 0.01); and to planning from intention (ß = 0.81, p < 0.01). In addition, there were significant model pathways to intention from instrumental attitude (ß = 0.28, p = 0.03), descriptive norm (ß = 0.09, p = 0.01), and PBC (ß = 0.52, p < 0.01). Overall, the TPB accounted for 69%, 63%, and 42% of the variance in intention, planning and PA, respectively.
The TPB appears to be a useful model for explaining PA in KCS. All TPB constructs except injunctive norm and affective attitude were useful for explaining intention with PBC emerging as the largest correlate. Developing PA interventions based on the TPB may be effective in promoting PA in KCS and may lead to important improvements in health.
PMCID: PMC3489870  PMID: 22866956
Exercise; Motivation; Social cognitive models; Correlates
21.  A randomized controlled trial on the effectiveness of strength training on clinical and muscle cellular outcomes in patients with prostate cancer during androgen deprivation therapy: rationale and design 
BMC Cancer  2012;12:123.
Studies indicate that strength training has beneficial effects on clinical health outcomes in prostate cancer patients during androgen deprivation therapy. However, randomized controlled trials are needed to scientifically determine the effectiveness of strength training on the muscle cell level. Furthermore, close examination of the feasibility of a high-load strength training program is warranted. The Physical Exercise and Prostate Cancer (PEPC) trial is designed to determine the effectiveness of strength training on clinical and muscle cellular outcomes in non-metastatic prostate cancer patients after high-dose radiotherapy and during ongoing androgen deprivation therapy.
Patients receiving androgen deprivation therapy for 9-36 months combined with external high-dose radiotherapy for locally advanced prostate cancer are randomized to an exercise intervention group that receives a 16 week high-load strength training program or a control group that is encouraged to maintain their habitual activity level. In both arms, androgen deprivation therapy is continued until the end of the intervention period.
Clinical outcomes are body composition (lean body mass, bone mineral density and fat mass) measured by Dual-energy X-ray Absorptiometry, serological outcomes, physical functioning (muscle strength and cardio-respiratory fitness) assessed with physical tests and psycho-social functioning (mental health, fatigue and health-related quality of life) assessed by questionnaires. Muscle cellular outcomes are a) muscle fiber size b) regulators of muscle fiber size (number of myonuclei per muscle fiber, number of satellite cells per muscle fiber, number of satellite cells and myonuclei positive for androgen receptors and proteins involved in muscle protein degradation and muscle hypertrophy) and c) regulators of muscle fiber function such as proteins involved in cellular stress and mitochondrial function. Muscle cellular outcomes are measured on muscle cross sections and muscle homogenate from muscle biopsies obtained from muscle vastus lateralis.
The findings from the PEPC trial will provide new knowledge on the effects of high-load strength training on clinical and muscle cellular outcomes in prostate cancer patients during androgen deprivation therapy.
Trial registration NCT00658229
PMCID: PMC3342229  PMID: 22458865
Strength training; Prostate cancer; Androgen deprivation therapy; Clinical and muscle cellular outcomes
22.  Physical activity type and intensity among rural breast cancer survivors: patterns and associations with fatigue and depressive symptoms 
Our study aims were to describe physical activity patterns and associations with fatigue and depressive symptoms among rural breast cancer survivors.
Population-based, mailed survey of 483 rural breast cancer survivors including the International Physical Activity Questionnaire (IPAQ).
With regard to type and intensity, domestic/gardening and moderate intensity accounted for the largest percentage of total energy expenditure (i.e., 60% and 69%, respectively). MET-mins/week variables were categorized as 0, > 0 to < 500, and ≥ 500 to reflect sedentary, insufficient, and meets current public health recommendations. After adjustment, fatigue was significantly associated with domestic/gardening (mean fatigue for sedentary, insufficient, and meets recommendations were 18.9, 16.4, and 13.4, respectively; p=.0019), leisure activity (means were 16.0, 14.5, and 11.8, respectively; p=.047), moderate intensity (means were 18.4, 16.7, and 13.7, respectively; p=.011), and daily minutes sitting (means for ≤ 120 min, > 120 to ≤ 360 min, and > 360 min of sitting were 12.5, 14.2, and 17.2, respectively; p=.0029). Fatigue was not associated with occupational, transportation, walking, or vigorous activity. After adjustment, only leisure activity was associated with depressive symptoms (means for sedentary, insufficient, and meets recommendations were 7.8, 7.7, and 6.2, respectively; p=.039).
Physical activity measurement tools that do not include domestic/gardening activities may underestimate physical activity in rural breast cancer populations. Physical activity associations with fatigue and depressive symptoms differed based on physical activity type and intensity suggesting hypotheses related to exercise effects on fatigue and depressive symptoms.
PMCID: PMC3041842  PMID: 21110134
Exercise; Oncology; Correlate; Predictor; Depression
23.  Predictors of adherence to an Iyengar yoga program in breast cancer survivors 
Despite the known health benefits of physical activity, participation rates in cancer survivor groups remain low. Researchers have attempted to identify alternative modes of nontraditional physical activities that may increase participation and adherence rates. This study investigated the determinants of yoga in breast cancer survivors.
To examine predictors of Iyengar yoga adherence in breast cancer survivors using the theory of planned behaviour. Settings and Design: Classes were held either in Campus Recreation facilities or at the Behavioral Medicine Fitness Center at the University of Alberta in Edmonton, Canada. The study was an evaluation of an existing yoga program.
Materials and Methods:
Twenty-three post adjuvant therapy breast cancer survivors participating in a community-based, twice weekly, 12 week Iyengar yoga program were asked to complete baseline measures of the theory of planned behavior, demographic, medical, health/fitness, and psychosocial variables. Adherence was measured by objective attendance to the classes.
Statistical Analysis:
We analyzed univariate associations between predictors and yoga adherence with independent t-tests.
Adherence to the Iyengar yoga program was 63.9% and was predicted by stronger intention (P<0.001), greater self-efficacy (P=0.003), more positive instrumental attitude (Ps=0.025), higher disease stage (P=0.018), yoga experience in the past year, (P=0.044), diagnosis of a second cancer (P=0.008), lower fatigue (P=0.037), and greater happiness (P=0.023).
Adherence to Iyengar yoga in breast cancer survivors was strongly related to motivational variables from the theory of planned behaviour. Researchers attempting to improve yoga adherence in breast cancer survivors may benefit from targeting the key constructs in the theory of planned behaviour.
PMCID: PMC3276930  PMID: 22346059
Iyengar yoga; breast cancer; survivorship; correlates; adherence; theory of planned behavior
24.  Determinants of quality of life in adults with type 1 and type 2 diabetes 
Limited evidence exists on the determinants of quality of life (QoL) specific to adults with type 1 diabetes (T1D). Further, it appears no study has compared the determinants of QoL between T1D and type 2 diabetes (T2D) groups. The objectives of this study were to examine: (1) determinants of QoL in adults with T1D; and, (2) differences in QoL determinants between T1D and T2D groups.
The Alberta Longitudinal Exercise and Diabetes Research Advancement (ALEXANDRA) study, a longitudinal study of adults with diabetes in Alberta, Canada. Adults (18 years and older) with T1D (N = 490) and T2D (N = 1,147) provided information on demographics (gender, marital status, education, and annual income), personality (activity trait), medical factors (diabetes duration, insulin use, number of comorbidities, and body mass index), lifestyle behaviors (smoking habits, physical activity, and diet), health-related quality of life (HRQL) and life satisfaction. Multiple regression models identified determinants of HRQL and life satisfaction in adults with T1D. These determinants were compared with determinants for T2D adults reported in a previous study from this population data set. Factors significantly associated with HRQL and life satisfaction in either T1D or T2D groups were further tested for interaction with diabetes type.
In adults with T1D, higher activity trait (personality) score (β = 0.28, p < 0.01), fewer comorbidities (β = -0.27, p < 0.01), lower body mass index (BMI)(β = -0.12, p < 0.01), being a non-smoker (β = -0.14, p < 0.01), and higher physical activity levels (β = 0.16, p < 0.01) were associated with higher HRQL. Having a partner (β = 0.11, p < 0.05), high annual income (β = 0.16, p < 0.01), and high activity trait (personality) score (β = 0.27, p < 0.01) were significantly associated with higher life satisfaction. There was a significant age × diabetes type interaction for HRQL. The T2D group had a stronger positive relationship between advancing age and HRQL compared to the T1D group. No interaction was significant for life satisfaction.
Health services should target medical and lifestyle factors and provide support for T1D adults to increase their QoL. Additional social support for socioeconomically disadvantaged individuals living with this disease may be warranted. Health practitioners should also be aware that age has different effects on QoL between T1D and T2D adults.
PMCID: PMC3258220  PMID: 22182307
quality of life; health-related quality of life; life satisfaction; type 1 diabetes; type 2 diabetes; adults with diabetes
25.  Lessons learned in the trenches: facilitating exercise adherence among breast cancer survivors in a group setting 
Cancer nursing  2010;33(6):E10-E17.
Improving effectiveness of group exercise counseling for breast cancer survivors is needed.
Describe clinical observations, with research and translation implications, derived during group exercise counseling for breast cancer survivors.
While implementing group session components of an effective social cognitive theory-based exercise intervention, observations were made through verbal discussion with study staff, review of participant feedback, and prospective journaling by the group facilitator. The intervention has been implemented 11 times (i.e., 63 survivors; 66 group sessions). Thematic consistency, application to intervention goals and design, and implications were reconciled between two investigators.
Breast cancer diagnosis was a strong source of commonality among group participants. Participant age, time since diagnosis, and expectation for group sessions (e.g., group support versus health education) hindered group commonality. Barriers unique to the breast cancer experience were infrequent but people-pleasing behavior was often identified as a barrier to adherence. Feeling at risk for cancer recurrence was a major concern. Some participants required referral for mental health evaluation for pre-existing conditions (e.g., depression). Although participants easily understood time management, application of other behavioral modification techniques was more difficult.
A breast cancer diagnosis alone is not sufficient for commonality among group members. Teaching time management and positive reframing is essential. Protocols for appropriate mental health referrals are needed.
Implications for Practice
Our observations will assist group leaders in enhancing group dynamics and addressing obstacles hindering counseling effectiveness. Moreover, our results suggest hypotheses related to enhancing behavior change in a group setting worthy of future study.
PMCID: PMC2943976  PMID: 20562618
oncology; physical activity; survivorship; social cognitive theory; health education

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