Exercise as Medicine in Cardio-Oncology: Reducing Health Disparities in Hispanic and Latina Breast Cancer Survivors.

PURPOSE OF REVIEW: This review aims to access the current state of the evidence in exercise as medicine for cardio-oncology in Hispanic and Latina breast cancer survivors and to provide our preliminary data on the effects of supervised aerobic and resistance training on cardiovascular disease (CVD) risk in this population. RECENT FINDINGS: Breast cancer survivors have a higher risk of CVD; particularly Hispanic and Latina breast cancer survivors have a higher burden than their White counterparts. Exercise has been shown to reduce CVD risk in breast cancer survivors; however, evidence in Hispanic and Latina breast cancer survivors is scarce. Our review highlights a clear need for exercise oncology clinical trials in Hispanic and Latina breast cancer survivors targeting CVD risk factors. Moreover, our exploratory results highlight that 16 weeks of aerobic and resistance training may reduce the 10-year risk of developing CVD by 15% in Hispanic and Latina breast cancer survivors.

Physical activity and physical fitness assessments in adolescents and young adults diagnosed with cancer: a scoping review.

PURPOSE: This scoping review describes the assessment methodologies for physical activity (PA) and physical fitness assessments used in studies focusing on adolescents and young adults (AYAs) diagnosed with cancer. METHODS: A search of the literature was conducted in PubMed, CINAHL, Web of Science, and Cochrane Library following the PRISMA-ScR statement. A total of 34 studies were included in this review. RESULTS: PA was primarily assessed via self-reported questionnaires (30/34) either completed in-person (n = 17) or online (n = 13) at different time points and different stages along the cancer trajectory (i.e., from diagnosis onward). A total of 9 studies conducted a physical fitness assessment. CONCLUSIONS: PA and physical fitness measurements are key when trying to describe outcomes, assess for associations, track changes, measure intervention adherence, and test intervention efficacy and effectiveness. Considerable heterogeneity across studies was reported limiting the generation of formal recommendations or guidance for researchers, healthcare providers, and policy makers.

High-intensity interval training improves metabolic syndrome in women with breast cancer receiving Anthracyclines.

INTRODUCTION: Anthracycline chemotherapy is a frequent treatment for breast cancer, whereas it can increase risk of physiologic side-effects, such as metabolic syndrome (MetS). Exercise has been used as a non-pharmacological strategy to decrease MetS. Specifically, high-intensity interval training (HIIT) has been shown to improve MetS in patients with diabetes or cardiac rehabilitation patients; however, the effects of HIIT on MetS and associated biomarkers in patients with breast cancer receiving anthracycline chemotherapy have not been previously explored. Therefore, we purposed to determine the effects of HIIT on MetS in breast cancer patients undergoing anthracycline chemotherapy. METHODS: In total, 30 patients with breast cancer were recruited prior to initiating treatment and randomized into HIIT (n = 15) or control (n = 15). The HIIT group attended supervised cycling sessions 3 days/week for 8 weeks. MetS was assessed by waist circumference, blood pressure, fasting levels of high-density lipoprotein cholesterol (HDL-C), triglycerides, and glucose. Circulating levels of MetS-related biomarkers were also measured (total cholesterol, insulin, HbA1c, leptin, adiponectin, and c-reactive protein). RESULTS: After 8 weeks, MetS z-score was significantly improved in the HIIT group compared with controls (-7.60, 95% CI: -9.08 to -6.13, p < 0.001). MetS variables (HDL-C, glucose, and triglycerides) and circulating levels of MetS-related biomarkers were significantly improved in the HIIT group compared with controls (p < 0.001). Non-significant differences were found in body composition outcomes at the end of the study. CONCLUSIONS: HIIT may be an effective strategy to improve MetS in breast cancer patients undergoing anthracycline chemotherapy. Furthermore, changes in MetS were independent of changes in body composition.

Long-term dietary intervention influence on physical activity in the Women's Health Initiative Dietary Modification randomized trial.

PURPOSE: In the Women's Health Initiative (WHI) Dietary Modification (DM) randomized trial, dietary intervention significantly reduced breast cancer mortality (P = 0.02). In observational studies, physical activity is associated with lower breast cancer incidence. Currently, dietary intervention influence on other health-related behaviors is unknown. Therefore, we evaluated whether the WHI dietary intervention influenced self-directed physical activity. METHODS: Of 48,835 postmenopausal women, 19,541 were randomized to dietary intervention (18 nutritionist-led group sessions first year, then quarterly sessions throughout 8.5 years [median] intervention) and 29,294 to a usual diet comparison (written health-related materials only). Neither randomization group received specific or ongoing instructions to increase physical activity. Episodes per week of moderate or vigorous recreational physical activity (MVPA) were serially reported. Marginal longitudinal logistic regression models were used to assess physically inactive (MVPA = 0) or physically active (MVPA > 0) participants by randomization group. Marginal Poisson regression models estimated mean weekly MVPA. RESULTS: At entry, 45.6% of all participants reported physical inactivity (MVPA = 0). In 43,760 women with MVPA information, throughout 15.9 years (median) cumulative follow-up, dietary intervention group participation was associated with 7% lower physical inactivity rate (odds ratio [OR] 0.93, 95% confidence interval [CI] 0.91, 0.95, P < 0.001) and a 4% higher mean MVPA (ratio of means [RM] 1.04 95% CI 1.02, 1.06, P < 0.001), relative to the comparison group. CONCLUSION: In a randomized trial setting, a low-fat dietary pattern intervention was associated with a long-term, favorable influence on self-directed recreational physical activity. TRIAL REGISTRATION: NCT00000611.

Interventions to Reduce Sedentary Behavior in Cancer Patients and Survivors: a Systematic Review.

PURPOSE OF REVIEW: Sedentary behaviors (SB) after cancer diagnosis are associated with poor prognosis for certain cancers, and cancer patients and survivors report high levels of SB. Reducing SB may be a feasible and effective intervention strategy to improve outcomes. This systematic review aims to identify and evaluate the literature on interventions to reduce SB in cancer patients and survivors. RECENT FINDINGS: Studies were identified via database searches in December 2020. Two authors evaluated study eligibility. Data were extracted and checked, and risk of bias was assessed by the study team. Of 1401 records identified, nine studies involving 394 cancer patients or survivors were included in this review. Six were randomized trials, three were non-randomized intervention studies, and almost all (n = 8) focused on feasibility with small sample sizes. All studies were conducted within the previous 5 years in Canada, Australia, USA, and South Korea. Cancer types studied were breast (n = 3), prostate (n = 2), colorectal or peritoneal (n = 1), and mixed types (n = 3). Intervention duration of 12 weeks was most common (n = 7). Five studies had multiple intervention components, and six studies included wearable devices to measure and/or prompt behavior change. There was an overall trend where intervention groups reduced SB vs. control groups, often coupled with an increase in moderate-to-vigorous physical activity. This review suggests that there is some promise for intervention strategies to reduce SB in cancer patients and survivors. There is a need for more high-quality randomized controlled trials to understand how to best decrease SB in cancer patients and survivors.

Cardiometabolic risk factors, physical activity, and postmenopausal breast cancer mortality: results from the Women's Health Initiative.

BACKGROUND: Higher physical activity levels are associated with lower breast cancer-specific mortality. In addition, the metabolic syndrome is associated with higher breast cancer-specific mortality. Whether the physical activity association with breast cancer mortality is modified by number of metabolic syndrome components (cardiometabolic risk factors) in postmenopausal women with early-stage breast cancer remains unknown. METHODS: Cardiovascular risk factors included high waist circumference, hypertension, high cholesterol, and diabetes. Breast cancers were verified by medical record review. Mortality finding were enhanced by serial National Death Index queries. Cox proportional hazards regression models were used to estimate associations between baseline physical activity and subsequent breast cancer-specific and overall mortality following breast cancer diagnosis in Women's Health Initiative participants. These associations were examined after stratifying by cardiometabolic risk factor group. RESULTS: Among 161,308 Women's Health Initiative (WHI) participants, 8543 breast cancers occurred after 9.5 years (median) follow-up in women, additionally with information on cardiometabolic risk factors and physical activity at entry. In multi-variable analyses, as measured from cancer diagnosis, higher physical activity levels were associated with lower all-cause mortality risk (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.78-0.95, trend P < 0.001) but not with breast cancer-specific mortality (HR 0.85, 95% CI 0.70 to 1.04, trend P = 0.09). The physical activity and all-cause mortality association was not significantly modified by cardiometabolic risk factor number. CONCLUSIONS: Among women with early-stage breast cancer, although higher antecedent physical activity was associated with lower risk of all-cause mortality, the association did not differ by cardiometabolic risk factor number.

Child physical activity as a modifier of the relationship between prenatal exposure to maternal overweight/obesity and neurocognitive outcomes in offspring.

BACKGROUND/OBJECTIVES: With rising obesity rates among pregnant women, more children are exposed in utero to maternal obesity. In prior epidemiological studies, exposure to maternal obesity was associated with lower intelligence quotient (IQ) scores and worse cognitive abilities in offspring. Further studies have shown that offspring exposed to maternal obesity, exhibit differences in the white matter microstructure properties, fractional anisotropy (FA) and mean diffusivity (MD). In contrast, physical activity was shown to improve cognition and white matter microstructure during childhood. We examined if child physical activity levels modify the relationship between prenatal exposure to maternal obesity with IQ and white matter microstructure in offspring. SUBJECTS/METHODS: One hundred children (59% girls) age 7-11 years underwent brain magnetic resonance imaging and IQ testing. Maternal pre-pregnancy BMI was abstracted from electronic medical records. White matter was assessed using diffusion tensor imaging with the measures, global FA, MD. The 3-day physical activity recall was used to measure moderate-to-vigorous physical activity and vigorous physical activity (VPA). Linear regression was used to test for interactions between prenatal exposure to maternal overweight/obesity and child PA levels on child IQ and global FA/MD. RESULTS: The relationship between prenatal exposure to maternal overweight/obesity and child IQ and global FA varied by child VPA levels. Children exposed to mothers with overweight/obesity who engaged in more VPA had higher IQ scores and global FA compared to exposed children who engaged in less VPA. Associations were independent of child age, sex, BMI Z-score and socioeconomic status. Children born to normal-weight mothers did not differ in either IQ or global FA by time in VPA. CONCLUSIONS: Our findings support findings in rodent models and suggest that VPA during childhood modifies the relationship between prenatal exposure to maternal obesity and child IQ and white matter microstructure.

Effect of high-intensity interval training on patient-reported outcomes and physical function in women with breast cancer receiving anthracycline-based chemotherapy.

PURPOSE: The purpose of this study was to determine the effects of an 8-week HIIT intervention on patient-reported outcomes and physical function in breast cancer patients undergoing anthracycline-based chemotherapy. METHODS: Thirty breast cancer patients were recruited prior to initiating treatment and randomized into the HIIT group (n = 15) or control (CON) group (n = 15). The HIIT group attended HIIT sessions three days per week for eight weeks. The CON group was asked to maintain their current level of physical activity. Patient-reported outcomes were assessed by the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B), Multidimensional Fatigue Inventory with 20 questions (MFI-20), and the 15-item Five-Facet Mindfulness Questionnaire (FFMQ-15). Physical function was assessed using the timed up and go (TUG), 30-s sit-to-stand (30STS), Margaria-Kalamen stair climb test, and 6-min walk test (6MWT). Repeated measures ANCOVA and paired t-tests were performed to assess group differences. RESULTS: All patients completed the 8-week study with 82.3% adherence to the intervention among the HIIT group. Post-intervention, significant improvements were found for the Margaria-Kalamen stair climb test (- 3.39%; P = 0.013) and 6MWT (+ 11.6%; P = 0.008) in the HIIT group compared to baseline and CON group. No changes in patient-reported outcomes, TUG, and 30STS were observed following the 8-week study period in both groups (P > 0.05). CONCLUSIONS: HIIT may be an effective strategy to improve physical function and possibly maintain QOL in breast cancer patients undergoing the anthracycline-based chemotherapy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT02454777.

Prehabilitative Exercise for the Enhancement of Physical, Psychosocial, and Biological Outcomes Among Patients Diagnosed with Cancer.

PURPOSE OF REVIEW: This review summarizes the effects of prehabilitative exercise interventions on the physical, psychosocial, and biological outcomes among patients with cancer. Current gaps and future directions in prehabilitative exercise research will be addressed. RECENT FINDINGS: Prehabilitative exercise mitigates the detrimental impact of cancer surgery on physical fitness, noted by increases in maximal oxygen consumption and 6-min walk distance. Beneficial effects on psychosocial and biological outcomes remain inconclusive. Aerobic exercise interventions were often prescribed and included low-, moderate-, or high-intensity exercise. Resistance exercise interventions were often performed in conjunction with aerobic exercise. Prehabilitative exercise elicits robust improvements in physical fitness; however, effect on psychosocial and biological outcomes remains inconclusive. Exercise prescription parameters varied greatly by frequency, intensity, time, and type across multiple cancer diagnoses. Future investigations are needed to systematically dose exercise for a wider variety of outcome measures, with an overall goal to set forth pre-operative exercise guidelines.

Hispanic ethnicity as a moderator of the effects of aerobic and resistance exercise in survivors of breast cancer.

BACKGROUND: Metabolic syndrome (MSY) is associated with an increased risk of cardiovascular disease, type 2 diabetes, and recurrence in breast cancer survivors (BCS). MSY is 1.5 times more common in Hispanic women compared with non-Hispanic women. Although exercise mitigates MSY in BCS, to the best of the authors' knowledge, few studies to date have focused on minorities. This secondary analysis examined ethnicity as a moderator of the effects of a 16-week aerobic and resistance exercise intervention on MSY, sarcopenic obesity, and serum biomarkers in BCS. METHODS: A total of 100 eligible BCS were randomized to exercise (50 BCS) or usual care (50 BCS). The exercise intervention promoted moderate to vigorous aerobic and resistance exercise 3 times a week for 16 weeks. MSY z scores, sarcopenic obesity, and serum biomarkers were measured at baseline, after the intervention, and at the 28-week follow-up (exercise group only). Linear mixed models adjusted for baseline values of the outcome, age, disease stage, adjuvant treatment, and recent physical activity were used to evaluate effect modification by ethnicity. RESULTS: The study sample was 57% Hispanic BCS (HBCS) and 43% non-Hispanic BCS (NHBCS). HBCS were younger, of greater adiposity, and had been diagnosed with more advanced cancers compared with NHBCS (P<.001). Ethnicity was found to moderate the mean differences in exercise training on triglycerides (-36.4 mg/dL; 95% confidence interval [95% CI],-64.1 to -18.8 mg/dL), glucose (-8.6 mg/dL; 95% CI, -19.1 to -3.0 mg/dL), and C-reactive protein (-3.3 mg/L; 95% CI, -7.3 to -0.9 mg/L). CONCLUSIONS: HBCS appear to have poorer metabolic profiles and therefore may derive relatively larger metabolic changes from exercise compared with NHBCS. Clinical exercise interventions may attenuate existing health disparities across diverse groups of BCS.

Effects of high-intensity interval training on vascular endothelial function and vascular wall thickness in breast cancer patients receiving anthracycline-based chemotherapy: a randomized pilot study.

PURPOSE: The purpose of this study was to determine the effects of an 8-week high-intensity interval training (HIIT) intervention on vascular endothelial function, measured as brachial artery flow-mediated dilation (baFMD), and vascular wall thickness measured by carotid intima media thickness (cIMT) in breast cancer patients undergoing anthracycline-based chemotherapy. METHODS: Thirty women were randomized to either HIIT or non-exercise control groups (CON). The HIIT group participated in an 8-week HIIT intervention occurring three times per week on a cycle ergometer. The CON group was offered the HIIT intervention after 8 weeks. baFMD was measured from the brachial artery diameter at baseline (D0) and 1 min after cuff deflation (D1); percent change was calculated by measuring brachial artery diameter after cuff deflation relative to the baseline [baFMD = (D1 - D0)/D0 × 100]. The cIMT was obtained from the posterior wall of common carotid artery 10 mm below the carotid bulb. Paired t test and repeated measures ANCOVA were performed to assess changes in baFMD and cIMT. RESULTS: At baseline, the HIIT (n = 15) and CON (n = 15) groups did not differ by age (46.9 ± 9.8 years), BMI (31.0 ± 7.5 kg/m2), and blood pressure (123.4 ± 16.8/72.3.9 ± 5.6 mmHg). Post-exercise, baFMD significantly increased [4.3; 95% confidence interval (CI): (1.5, 7.0), p = 0.005] in HIIT versus CON group. cIMT did not significantly change [0.003, 95% CI - 0.004, 0.009), p = 0.40] in HIIT group, while IMT significantly increased from baseline to post-intervention (0.009, 95% CI 0.004, 0.010, p = 0.003) in CON group. CONCLUSION: This study may suggest that HIIT improved vascular endothelial function and maintained wall thickness in breast cancer patients undergoing anthracycline-based chemotherapy. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02454777.

Feasibility of high intensity interval training in patients with breast Cancer undergoing anthracycline chemotherapy: a randomized pilot trial.

BACKGROUND: Anthracycline-based chemotherapy is associated with reduced cardiorespiratory fitness in breast cancer patients. High intensity interval training (HIIT) induces greater benefits on cardiorespiratory fitness than moderate continuous aerobic exercise in patients with heart failure. The study purpose was to determine whether a HIIT intervention is a feasible exercise strategy for breast cancer patients undergoing anthracycline-based chemotherapy. METHODS: Thirty women were randomized to either HIIT or non-exercise control group (CON). Participants performed a maximal cycling fitness test to measure peak power output during maximal oxygen uptake (VO2max). The HIIT group participated in an 8-week HIIT intervention occurring 3 times weekly. Feasibility was calculated by computing (1) the average weekly minutes of HIIT over 8 weeks and (2) the number of sessions attended and multiplied by 100 (percentage of sessions). The intervention was considered feasible if more than 50% of participants completed both an average of 70% of weekly minutes (63/90 min) and attended 70% exercise sessions (17/24 sessions). RESULTS: Participants were 46.9 ± 9.8 (mean ± SD) years old, diagnosed with clinical stage II (30%) or III (63%) breast cancer. The average weekly minutes of exercise completed was 78 ± 5.1 out of 90 min. Twelve of 15 participants met both feasibility criteria, attending 19.2 ± 2.1 out of 24 sessions (82.3%). VO2max was maintained (19.7 ± 8.7 to 19.4 ± 6.6 ml/kg/min) in HIIT group (p = 0.94) while there was a significant decrease in VO2max (18.7 ± 7.1 to 16.1 ± 6.0 ml/kg/min) in CON group from baseline to 8 weeks (p = 0.001). CONCLUSIONS: HIIT is a feasible exercise intervention to maintain VO2max in breast cancer patients receiving anthracycline-based chemotherapy. TRIAL REGISTRATION: The protocol and informed consent were approved by the institutional IRB (HS-12-00227) and registered ( ClinicalTrials.gov NCT02454777; date of registration: May 272,015).

The Impact of Obesity on Breast Cancer Diagnosis and Treatment.

PURPOSE OF REVIEW: Obesity is a recognized risk factor for the development of breast cancer and recurrence even when patients are treated appropriately. We reviewed the literature that addresses the impact of obesity on diagnosis and the individual therapeutic interventions, and present a summary of the findings. RECENT FINDINGS: Compared to non-obese women with breast cancer, obese women with breast cancer have a worse disease-free and overall survival despite appropriate local and systemic therapies. In brief, obese breast cancer patients experience more complications related to surgery, radiation, and chemotherapy. Further, obese patients are at increased risk for local recurrence compared to normal-weight women. Similarly, systemic chemotherapy is less effective, even when dosed appropriately on the basis of actual weight. Overall, endocrine therapy is less effective in obese women, and there is a suggestion that aromatase inhibitors may be selectively less effective than tamoxifen. Obese women are less likely to undergo breast reconstruction than normal-weight women, and those who do have surgery experience more surgical complications. The efficacy of cancer treatments is significantly lower in obese breast cancer survivors, posing greater challenges in patient care and disease management in this patient population. Further investigations are warranted to assess the effects on treatment outcomes and optimize therapeutic mechanisms in order to successfully target breast cancer associated with obesity.

Aerobic and resistance exercise improves physical fitness, bone health, and quality of life in overweight and obese breast cancer survivors: a randomized controlled trial.

BACKGROUND: Exercise is an effective strategy to improve quality of life and physical fitness in breast cancer survivors; however, few studies have focused on the early survivorship period, minorities, physically inactive and obese women, or tested a combined exercise program and measured bone health. Here, we report the effects of a 16-week aerobic and resistance exercise intervention on patient-reported outcomes, physical fitness, and bone health in ethnically diverse, physically inactive, overweight or obese breast cancer survivors. METHODS: One hundred breast cancer survivors within 6 months of completing adjuvant treatment were assessed at baseline, post-intervention, and 3-month follow-up (exercise group only) for physical fitness, bone mineral density, serum concentrations of bone biomarkers, and quality of life. The exercise intervention consisted of moderate-vigorous (65-85% heart rate maximum) aerobic and resistance exercise thrice weekly for 16 weeks. Differences in mean changes for outcomes were evaluated using mixed-model repeated measure analysis. RESULTS: At post-intervention, the exercise group was superior to usual care for quality of life (between group difference: 14.7, 95% CI: 18.2, 9.7; p < 0.001), fatigue (p < 0.001), depression (p < 0.001), estimated VO2max (p < 0.001), muscular strength (p < 0.001), osteocalcin (p = 0.01), and BSAP (p = 0.001). At 3-month follow-up, all patient-reported outcomes and physical fitness variables remained significantly improved compared to baseline in the exercise group (p < 0.01). CONCLUSIONS: A 16-week combined aerobic and resistance exercise program designed to address metabolic syndrome in ethnically-diverse overweight or obese breast cancer survivors also significantly improved quality of life and physical fitness. Our findings further support the inclusion of supervised clinical exercise programs into breast cancer treatment and care. TRIAL REGISTRATION: This trial is registered on ClinicalTrials.gov: NCT01140282 as of June 9, 2010.

Adipose tissue inflammation in breast cancer survivors: effects of a 16-week combined aerobic and resistance exercise training intervention.

PURPOSE: Obesity is a leading modifiable contributor to breast cancer mortality due to its association with increased recurrence and decreased overall survival rate. Obesity stimulates cancer progression through chronic, low-grade inflammation in white adipose tissue, leading to accumulation of adipose tissue macrophages (ATMs), in particular, the pro-inflammatory M1 phenotype macrophage. Exercise has been shown to reduce M1 ATMs and increase the more anti-inflammatory M2 ATMs in obese adults. The purpose of this study was to determine whether a 16-week exercise intervention would positively alter ATM phenotype in obese postmenopausal breast cancer survivors. METHODS: Twenty obese postmenopausal breast cancer survivors were randomized to a 16-week aerobic and resistance exercise (EX) intervention or delayed intervention control (CON). The EX group participated in 16 weeks of supervised exercise sessions 3 times/week. Participants provided fasting blood, dual-energy X-ray absorptiometry (DXA), and superficial subcutaneous abdominal adipose tissue biopsies at baseline and following the 16-week study period. RESULTS: EX participants experienced significant improvements in body composition, cardiometabolic biomarkers, and systemic inflammation (all p < 0.03 vs. CON). Adipose tissue from EX participants showed a significant decrease in ATM M1 (p < 0.001), an increase in ATM M2 (p < 0.001), increased adipose tissue secretion of anti-inflammatory cytokines such as adiponectin, and decreased secretion of the pro-inflammatory cytokines IL-6 and TNF- α (all p < 0.055). CONCLUSIONS: A 16-week aerobic and resistance exercise intervention attenuates adipose tissue inflammation in obese postmenopausal breast cancer survivors. Future large randomized trials are warranted to investigate the impact of exercise-induced reductions in adipose tissue inflammation and breast cancer recurrence.

Impact of resistance training on body composition and metabolic syndrome variables during androgen deprivation therapy for prostate cancer: a pilot randomized controlled trial.

BACKGROUND: Prostate cancer patients on androgen deprivation therapy (ADT) experience adverse effects such as lean mass loss, known as sarcopenia, fat gain, and changes in cardiometabolic factors that increase risk of metabolic syndrome (MetS). Resistance training can increase lean mass, reduce body fat, and improve physical function and quality of life, but no exercise interventions in prostate cancer patients on ADT have concomitantly improved body composition and MetS. This pilot trial investigated 12 weeks of resistance training on body composition and MetS changes in prostate cancer patients on ADT. An exploratory aim examined if a combined approach of training and protein supplementation would elicit greater changes in body composition. METHODS: Prostate cancer patients on ADT were randomized to resistance training and protein supplementation (TRAINPRO), resistance training (TRAIN), protein supplementation (PRO), or control stretching (STRETCH). Exercise groups (EXE = TRAINPRO, TRAIN) performed supervised exercise 3 days per week for 12 weeks, while non-exercise groups (NoEXE = PRO, STRETCH) performed a home-based stretching program. TRAINPRO and PRO received 50 g⋅day- 1 of whey protein. The primary outcome was change in lean mass assessed through dual energy x-ray absorptiometry. Secondary outcomes examined changes in sarcopenia, assessed through appendicular skeletal mass (ASM) index (kg/m2), body fat %, strength, physical function, quality of life, MetS score and the MetS components of waist circumference, blood pressure, glucose, high-density lipoprotein-cholesterol, and triglyceride levels. RESULTS: A total of 37 participants were randomized; 32 participated in the intervention (EXE n = 13; NoEXE n = 19). At baseline, 43.8% of participants were sarcopenic and 40.6% met the criteria for MetS. Post-intervention, EXE significantly improved lean mass (d = 0.9), sarcopenia prevalence (d = 0.8), body fat % (d = 1.1), strength (d = 0.8-3.0), and prostate cancer-specific quality of life (d = 0.9) compared to NoEXE (p < 0.05). No significant differences were observed between groups for physical function or MetS-related variables except waist circumference (d = 0.8). CONCLUSIONS: A 12-week resistance training intervention effectively improved sarcopenia, body fat %, strength and quality of life in hypogonadal prostate cancer patients, but did not change MetS or physical function. PRO did not offer additional benefit in improving body composition. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01909440 . Registered 24 July 2013.

Objective physical and mental markers of self-reported fatigue in women undergoing (neo)adjuvant chemotherapy for early-stage breast cancer.

BACKGROUND: Objective, treatment-independent markers of cancer-related fatigue are needed to advance clinical trials. In the current study, the authors evaluated physical, neurocognitive, and serologic markers for correlation with self-reported fatigue before and after (neo)adjuvant chemotherapy for patients with early-stage breast cancer. METHODS: Women with AJCC TNM Stage I-III breast cancer consented to assessment before and after the completion of 4 cycles of dose-dense doxorubicin and cyclophosphamide. Assessment included self-reported fatigue (using the Brief Fatigue Inventory), depression (using the Center for Epidemiologic Studies-Depression Scale [CES-D]), Pittsburgh Sleep Quality Index, and 28 objective measures (grip strength in dominant and nondominant hands, 6-minute walk, daily total energy expenditure, 14 neurocognitive tests, and 10 serologic markers). Generalized linear regression models of fatigue were constructed (1 model per marker), and adjusted for depression, timing before/after chemotherapy, menopausal status, obesity, and educational level. P values were adjusted to control the False Discovery Rate. RESULTS: Of 28 subjects, 3 withdrew without completing baseline assessments. Prechemotherapy and postchemotherapy data were available for the evaluation of physical measures (25 subjects aged 50.6 ± 9.5 years), neurocognitive tests (22 subjects), and serologic markers (10 subjects). On covariate-adjusted analysis, interleukin (IL)-12 was found to be associated with fatigue at both assessments (P<.01). Serum eotaxin (P < .01), IL-1RA (P < .01), monocyte chemoattractant protein 1 (MCP-1) (P<.01), and performance on 2 neurocognitive (Trail Making) tests (P<.01 and P = .02, respectively) were found to be inversely associated with fatigue before chemotherapy but not afterward, whereas daily energy expenditure, serum MCP-1, and serum macrophage inflammatory protein 1a (MIP-1a) were found to be associated with fatigue after receipt of chemotherapy but not before (P<.01 for each). The association between energy expenditure and fatigue was detectable only if an actively athletic subject with outlier values of energy expenditure was excluded. CONCLUSIONS: Serum IL-12 merits confirmatory testing as an objective, treatment-independent measure of fatigue in patients with early-stage breast cancer. Cancer 2017;123:1810-1816. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

An observational study to examine changes in metabolic syndrome components in patients with breast cancer receiving neoadjuvant or adjuvant chemotherapy.

BACKGROUND: The authors sought to determine the effect of chemotherapy on the development of metabolic syndrome (MetS) in premenopausal and postmenopausal women undergoing (neo)adjuvant therapy for early-stage breast cancer. METHODS: A total of 86 women with early-stage (AJCC stage I-III) breast cancer who were free from clinically diagnosed MetS (defined as 3 of 5 components of MetS) were prospectively tested for the presence of the 5 components of MetS within 1 week before initiating and after completing (neo)adjuvant chemotherapy. The 5 components of MetS measured were waist circumference; blood pressure; and fasting levels of blood glucose, triglycerides, and high-density lipoprotein cholesterol. Anthropometrics (body weight, percentage body fat, fat mass), lipid profile (total cholesterol, low-density lipoprotein cholesterol), glucose metabolism (insulin, homeostatic model assessment of insulin resistance, glycated hemoglobin), and inflammation (C-reactive protein) also were examined before initiating and after completing treatment. RESULTS: The current study included 46 premenopausal and 40 postmenopausal women. All individual MetS components and the overall MetS score were found to be statistically significantly increased (P<.01) after chemotherapy. Body weight, percentage body fat, fat mass, lipids, glucose metabolism, and inflammation also were found to be statistically significantly increased (P<.01). CONCLUSIONS: A 12-week to 18-week course of chemotherapy appears to statistically significantly increase MetS and related anthropometrics, biomarkers of glucose metabolism, and inflammation in patients with early-stage breast cancer with no preexisting MetS. Lifestyle interventions such as diet and exercise may be preventive approaches for use during chemotherapy to reduce the onset of MetS in patients with breast cancer. Cancer 2016. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. Cancer 2016;122:2646-2653. © 2016 American Cancer Society.

Acute Response of PGC-1α and IGF-1 Isoforms to Maximal Eccentric Exercise in Skeletal Muscle of Postmenopausal Women.

PGC-1α4, a novel isoform of the transcriptional coactivator PGC-1α, was recently postulated to modulate the expression of anabolic and catabolic genes and therefore regulate skeletal muscle hypertrophy. Resting levels of PGC-1α4 messenger RNA (mRNA) expression were found to increase in healthy adults after resistance training. However, the acute effect of resistance exercise (RE) on PGC-1α4 expression in populations prone to progressive muscle loss, such as postmenopausal women, has not been evaluated. Here, we investigated alterations in mRNA expression of PGC-1α4 and PGC-1α1, a regulator of muscle oxidative changes, in postmenopausal women after high-intensity eccentric RE and analyzed these findings with respect to changes in insulin-like growth factor (IGF)-1 and catabolic gene expression. Nine postmenopausal women (age, 57.9 ± 3.2 years) performed 10 sets of 10 maximal eccentric repetitions of single-leg extension with 20-second rest periods between sets. Muscle biopsies were obtained from the vastus lateralis of the exercised leg before and 4 hours after the RE bout with mRNA expression determined by quantitative real-time polymerase chain reaction. No significant changes in the mRNA expression of either PGC-1α isoform were observed after acute eccentric RE (p > 0.05). IGF-1Ea mRNA expression significantly increased (p ≤ 0.05), whereas IGF-1Eb and mechano-growth factor (MGF) did not significantly change (p > 0.05). PGC-1α4 mRNA expression was associated with reduced mRNA expression of the catabolic gene myostatin (R = -0.88, p < 0.01), whereas MGF mRNA expression was associated with reduced mRNA expression of the catabolic gene FOXO3A (R = -0.81, p ≤ 0.05). These data demonstrate an attenuated response of PGC-1α isoforms to an acute bout of maximal eccentric exercise with short rest periods in postmenopausal women.

Randomized controlled trial to evaluate the effects of combined progressive exercise on metabolic syndrome in breast cancer survivors: rationale, design, and methods.

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.