Time-Restricted Eating in Breast Cancer Survivors: Effects on Body Composition and Nutritional Status.

In this secondary analysis of an 8-wk single-arm feasibility study of weekday time-restricted eating (TRE), we explored the effects of TRE on body composition. Women (n = 22; ≥60 yr) who had completed chemotherapy for early-stage breast cancer and had a body mass index ≥25 kg/m2 were enrolled. Bioelectrical impedance analysis was performed before and after 8 wk of TRE, and nutritional status was evaluated by bioelectrical impedance vector analysis (BIVA). Body weight (p = 0.01) and total fat mass (p = 0.04) decreased with TRE. Phase angle was low (defined as ≤5.6°) in 86% of participants at baseline and did not change. Four participants who initially presented with obesity (>95% ellipse, BIVA) had favorable body composition modifications after TRE. Our study highlighted a less favorable body composition profile, poorer cell integrity and overhydration in these patients. BIVA was a useful method to assess body composition and hydration. A short TRE intervention was associated with decreased estimated fat mass and a favorable change in nutritional status in those with obesity.

Longitudinal Changes in Skeletal Muscle Metabolism, Oxygen Uptake, and Myosteatosis During Cardiotoxic Treatment for Early-Stage Breast Cancer.

BACKGROUND: While cardiotoxic chemotherapy is known to negatively impact cardiac function and hemoglobin levels, the impact on skeletal muscle has been understudied among patients. The purpose was to longitudinally characterize myosteatosis (muscle fat), skeletal muscle metabolism, and oxygen (O2) consumption during cardiotoxic chemotherapy for breast cancer. PATIENTS AND METHODS: Thirty-four patients with stage I-III breast cancer were enrolled before trastuzumab-containing and/or anthracycline-containing chemotherapy. We used magnetic resonance imaging to non-invasively quantify thigh myosteatosis (fat-water imaging), and lower leg metabolism (31P spectroscopy), O2 consumption (custom techniques), and peak power output during single-leg plantarflexion exercise at pre-, mid-, end-chemotherapy, and 1-year. We also measured pulmonary VO2peak and maximal leg press strength. RESULTS: During chemotherapy, VO2peak and leg press strength decreased while peak plantarflexion power output was maintained. At mid-chemotherapy, hemoglobin decreased (16%) and lower leg blood flow increased (37%) to maintain lower leg O2 delivery; exercise Pi:PCr and myosteatosis increased. Between mid- and end-chemotherapy, lower leg O2 extraction (28%) and O2 consumption (21%) increased, while plantarflexion exercise efficiency (watts/O2 consumed) decreased. At one year, VO2peak and leg press strength returned to pre-chemotherapy levels, but lower leg exercise O2 extraction, consumption and Pi:PCr, and myosteatosis remained elevated. CONCLUSION: Lower leg skeletal muscle blood flow and O2 extraction adapt to compensate for chemotherapy-related hemoglobin reduction for small muscle mass exercise but are insufficient to maintain large muscle mass exercise (pulmonary VO2peak, leg press strength). The excess O2 required to perform work, increased Pi:PCr ratio and myosteatosis together suggest suppressed fat oxidation during chemotherapy.

Cardiometabolic health impacts of time-restricted eating: implications for type 2 diabetes, cancer and cardiovascular diseases.

PURPOSE OF REVIEW: Time-restricted eating (TRE) entails consuming energy intake within a 4- to 10-h window, with the remaining time spent fasting. Although studies have reported health benefits from TRE, little is known about the impact of TRE on common chronic diseases such as type 2 diabetes, cancer and cardiovascular disease. This review summarizes and critically evaluates the most recent TRE research findings relevant to managing and treating these chronic diseases. RECENT FINDINGS: Most recent TRE studies have been in populations with overweight/obesity or metabolic syndrome; two have been in populations with diabetes, three in cancer survivors and none in populations with cardiovascular disease. Collectively, these studies showed that participants could adhere to TRE and TRE is well tolerated. These studies also showed preliminary efficacy for improved glucose regulation and insulin sensitivity, a reduction in body fat and blood pressure, reduced cardiovascular risk scores and increased quality of life. More research is required to define the most effective TRE protocol (i.e. length and timing of eating window, intervention duration). SUMMARY: TRE has demonstrated benefits on cardiovascular, metabolic and clinical outcomes relevant to the underlying pathophysiology, but there are limited data on TRE implemented specifically within populations with diabetes, cancer or cardiovascular disease.

Prevalence of Breast Cancer Survivors Among Canadian Women.

BACKGROUND: The 49% decrease in breast cancer mortality since 1986 has increased the number of breast cancer survivors requiring survivorship care. The purpose of this analysis was to estimate the 2022 prevalence of breast cancer survivors diagnosed within the past 15 years among Canadian women. METHODS: We extracted the projected female breast cancer cases from 2007 to 2021 and rates of net survival (competing noncancer causes of death removed) from the Canadian Cancer Society's statistical reports. Overall survival was extracted from published Ontario data. Using known survival rates for 1, 5, 10, and 15 years, we interpolated remaining years and applied the corresponding net and overall survival rates to the projected cases for each year from 2007 to 2021 to determine survivors in 2022. Prevalence for predefined age groups was also calculated. As an example of excess healthcare costs attributable to breast cancer, we calculated the excess costs of heart failure hospitalizations. RESULTS: From 2007 to 2021, there were 370,756 breast cancer cases. Using net survival, 318,429 (85.9%) of these patients were projected to survive breast cancer by 2022, a prevalence of 2.1% of Canadian women. Using overall survival, prevalence was 1.8%. Prevalence increased with age group, from 0.01% of those aged 20 to 24 years to 12.7% of those aged ≥90 years, and from 1.0% among the working and/or child-raising (age 20-64 years) to 5.4% among elderly populations (age ≥65 years). Among these survivors, 24.9% of projected heart failure hospitalizations would be in excess of those among matched control subjects, with projected excess costs of $16.5 million CAD. Given the excess healthcare costs, potential for reduced contributions to the workforce, and reduced quality of life associated with long-term impairments and risk of excess non-breast cancer death, enhanced breast cancer survivorship care is warranted. CONCLUSIONS: With an overall prevalence of 2% among Canadian women, breast cancer survivors represent an increasing segment of the working-age and elderly populations.

Rationale and design of the Diet Restriction and Exercise-induced Adaptations in Metastatic breast cancer (DREAM) study: a 2-arm, parallel-group, phase II, randomized control trial of a short-term, calorie-restricted, and ketogenic diet plus exercise during intravenous chemotherapy versus usual care.

BACKGROUND: An underlying cause of solid tumor resistance to chemotherapy treatment is diminished tumor blood supply, which leads to a hypoxic microenvironment, dependence on anaerobic energy metabolism, and impaired delivery of intravenous treatments. Preclinical data suggest that dietary strategies of caloric restriction and low-carbohydrate intake can inhibit glycolysis, while acute exercise can transiently enhance blood flow to the tumor and reduce hypoxia. The Diet Restriction and Exercise-induced Adaptations in Metastatic Breast Cancer (DREAM) study will compare the effects of a short-term, 50% calorie-restricted and ketogenic diet combined with aerobic exercise performed during intravenous chemotherapy treatment to usual care on changes in tumor burden, treatment side effects, and quality of life. METHODS: Fifty patients with measurable metastases and primary breast cancer starting a new line of intravenous chemotherapy will be randomly assigned to usual care or the combined diet and exercise intervention. Participants assigned to the intervention group will be provided with food consisting of 50% of measured calorie needs with 80% of calories from fat and ≤ 10% from carbohydrates for 48-72 h prior to each chemotherapy treatment and will perform 30-60 min of moderate-intensity cycle ergometer exercise during each chemotherapy infusion, for up to six treatment cycles. The diet and exercise durations will be adapted for each chemotherapy protocol. Tumor burden will be assessed by change in target lesion size using axial computed tomography (primary outcome) and magnetic resonance imaging (MRI)-derived apparent diffusion coefficient (secondary outcome) after up to six treatments. Tertiary outcomes will include quantitative MRI markers of treatment toxicity to the heart, thigh skeletal muscle, and liver, and patient-reported symptoms and quality of life. Exploratory outcome measures include progression-free and overall survival. DISCUSSION: The DREAM study will test a novel, short-term diet and exercise intervention that is targeted to mechanisms of tumor resistance to chemotherapy. A reduction in lesion size is likely to translate to improved cancer outcomes including disease progression and overall survival. Furthermore, a lifestyle intervention may empower patients with metastatic breast cancer by actively engaging them to play a key role in their treatment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03795493 , registered 7 January, 2019.

Rising to the challenge: designing, implementing and reporting exercise oncology trials in understudied populations.

Exercise can improve cancer-related fatigue, quality of life and physical fitness, but is understudied in less common cancers such as multiple myeloma. Studying less common cancers and the adoption of novel study designs and open-science practices would improve the generalisability, transparency, rigour, credibility and reproducibility of exercise oncology research.

Supervised, Multimodal Exercise: The Chemotherapy Supportive Therapy That Almost Does It All.

This commentary describes and places the results into context for the recent OptiTrain trial, a three­arm randomized trial of two different exercise interventions versus usual care on rates of chemotherapy completion, hospitalization, and hematological toxicity.

Exercise Intolerance in Anthracycline-Treated Breast Cancer Survivors: The Role of Skeletal Muscle Bioenergetics, Oxygenation, and Composition.

BACKGROUND: Peak oxygen consumption (VO2 ) is reduced in women with a history of breast cancer (BC). We measured leg blood flow, oxygenation, bioenergetics, and muscle composition in women with BC treated with anthracycline chemotherapy (n = 16, mean age: 56 years) and age- and body mass index-matched controls (n = 16). MATERIALS AND METHODS: Whole-body peak VO2 was measured during cycle exercise. 31 Phosphorus magnetic resonance (MR) spectroscopy was used to measure muscle bioenergetics during and after incremental to maximal plantar flexion exercise (PFE). MR imaging was used to measure lower leg blood flow, venous oxygen saturation (Sv O2 ), and VO2 during submaximal PFE, and abdominal, thigh, and lower leg intermuscular fat (IMF) and skeletal muscle (SM). RESULTS: Whole-body peak VO2 was significantly lower in BC survivors versus controls (23.1 ± 7.5 vs. 29.5 ± 7.7 mL/kg/minute). Muscle bioenergetics and mitochondrial oxidative capacity were not different between groups. No group differences were found during submaximal PFE for lower leg blood flow, Sv O2 , or VO2 . The IMF-to-SM ratio was higher in the thigh and lower leg in BC survivors (0.36 ± 0.19 vs. 0.22 ± 0.07, p = .01; 0.10 ± 0.06 vs. 0.06 ± 0.02, p = .03, respectively) and were inversely related to whole-body peak VO2 (r = -0.71, p = .002; r = -0.68, p = .003, respectively). In the lower leg, IMF-to-SM ratio was inversely related to VO2 and O2 extraction during PFE. CONCLUSION: SM bioenergetics and oxidative capacity in response to PFE are not impaired following anthracycline treatment. Abnormal SM composition (increased thigh and lower leg IMF-to-SM ratio) may be an important contributor to reduced peak VO2 during whole-body exercise among anthracycline-treated BC survivors. IMPLICATIONS FOR PRACTICE: Peak oxygen consumption (peak VO2 ) is reduced in breast cancer (BC) survivors and is prognostic of increased risk of cardiovascular disease-related and all-cause mortality. Results of this study demonstrated that in the presence of deficits in peak VO2 1 year after anthracycline therapy, skeletal muscle bioenergetics and oxygenation are not impaired. Rather, body composition deterioration (e.g., increased ratio of intermuscular fat to skeletal muscle) may contribute to reduced exercise tolerance in anthracycline BC survivors. This finding points to the importance of lifestyle interventions including caloric restriction and exercise training to restore body composition and cardiovascular health in the BC survivorship setting.

Exercise training affects hemodynamics not cardiac function during anthracycline-based chemotherapy.

INTRODUCTION: Preclinical data demonstrate the potential for exercise training to protect against anthracycline-related cardiotoxicity, but this remains to be shown in humans. PURPOSE: To assess whether exercise training during anthracycline-based chemotherapy for treatment of breast cancer affects resting cardiac function and hemodynamics. METHODS: In this prospective, non-randomized controlled study, 26 women who participated in aerobic and resistance training 3×/wk during chemotherapy were compared to 11 women receiving usual care. Two-dimensional echocardiography was performed before and 7-14 days after completion of anthracycline-based chemotherapy. Pre- and post-anthracycline cardiac function and hemodynamic variables were compared within each group with paired t-tests; the change was compared between groups using ANCOVA with adjustment for baseline values. RESULTS: Left ventricular longitudinal strain, volumes, ejection fraction, E/A ratio, and mass did not change in either group. Hemoglobin, hematocrit, and mean arterial pressure decreased significantly from baseline in both groups (all p < 0.05) with no differences between groups. Cardiac output increased in the usual care group only (+ 0.27 ± 0.24 L/min/m2, p < 0.01), which differed significantly from the exercise group (p = 0.03). Systemic vascular resistance (SVR) decreased in both groups (usual care: - 444, p < 0.01; exercise: - 265, dynes/s/cm5, p = 0.01). However, the reduction in SVR was significantly attenuated in the exercise group (p = 0.03) perhaps due to a compensatory decrease in estimated vessel lumen radius. CONCLUSION: Exercise training during anthracycline chemotherapy treatment had no effect on resting cardiac function but appeared to modify hemodynamic responses. Specifically, exercise training attenuated the drop in SVR in response to chemotherapy-related reductions in hematocrit potentially by increasing vessel lumen radius.

Impact of Exercise on Chemotherapy Tolerance and Survival in Early-Stage Breast Cancer: A Nonrandomized Controlled Trial.

BACKGROUND: Available preliminary evidence is conflicting on whether exercise can positively influence antineoplastic treatment tolerance and in turn improve survival. PATIENTS AND METHODS: This study compared chemotherapy treatment tolerance and survival among women receiving adjuvant chemotherapy for early-stage breast cancer who participated in a single-arm trial of supervised aerobic and resistance exercise programming versus a historical cohort that did not receive structured exercise programming. RESULTS: The exercise group (EX; n=73) and control group (CTR; n=85) participants were matched on age and treatment and balanced on medical history, cancer diagnosis, and body mass index. Attendance in the EX group was 64% ± 27% of 3 offered sessions per week. For all chemotherapy agents combined, the relative risk (RR) of a chemotherapy dose reduction (RR, 0.78; 95% CI, 0.54-1.11) or delay (RR, 1.05; 95% CI, 0.62-1.80) did not differ between groups. However, the EX group had reduced relative and absolute risks of a dose reduction in doxorubicin by 60% and 18%, respectively. For all agents combined, there were no differences between groups in risk of anemia, neutropenia, or weight gain. In the EX group, dose reductions due to neutropenia (P=.027), other infections (P=.049), and fatigue (P=.037) were less common, whereas mucositis was more common (P=.023), compared with the CTR group. The EX group had reduced relative and absolute risks of weight gain on the docetaxel + cyclophosphamide regimen by 38% and 30%, respectively. After a median follow-up of 70 months (range, 54-84 months), there was no difference between the EX and CTR groups in disease-free survival events (n=8 [11%] vs n=9 [11%], respectively; log-rank test, P=.78) or overall survival events (n=5 [7%] vs n=6 [7%], respectively; log-rank test, P=.974). CONCLUSIONS: Overall, exercise programming during adjuvant chemotherapy does not appear to impact treatment tolerance or survival in women receiving common modern regimens of adjuvant chemotherapy for early-stage breast cancer. However, exercise may provide selective benefits, depending on the treatment regimen received.

A Longitudinal Study of the Association of Clinical Indices of Cardiovascular Autonomic Function with Breast Cancer Treatment and Exercise Training.

BACKGROUND: Cardiovascular autonomic dysfunction is an early marker for cardiovascular disease. Anthracycline chemotherapy and left-sided radiation for breast cancer are associated with negative autonomic function changes. This study's objectives were to characterize changes in, and the association of exercise training with, clinical indices of cardiovascular autonomic function across the trajectory of breast cancer therapy. SUBJECTS, MATERIALS, AND METHODS: Seventy-three patients receiving adjuvant chemotherapy participated to varying degrees in supervised aerobic and resistance exercise during chemotherapy ± radiation and for 20 weeks after. Resting heart rate (HRrest) and blood pressure were measured weekly during chemotherapy. HRrest, exercise heart rate recovery (HRrecovery), and aerobic fitness were measured at enrollment, end of chemotherapy ± radiation, and 10 and 20 weeks after treatment. RESULTS: During chemotherapy, HRrest increased in a parabolic manner within a single treatment and with increasing treatment dose, whereas systolic and diastolic blood pressure decreased linearly across treatments. Tachycardia and hypotension were present in 32%-51% of participants. Factors associated with weekly changes during chemotherapy included receiving anthracyclines or trastuzumab, days since last treatment, hematocrit, and exercise attendance. Receipt of anthracyclines, trastuzumab, and left-sided radiation individually predicted impairments of HRrest and HRrecovery during chemotherapy ± radiation; however, aerobic fitness change and at least twice-weekly exercise attendance predicted improvement. By 10 weeks after treatment, HRrest and blood pressure were not different from prechemotherapy. CONCLUSION: In this study, chemotherapy resulted in increased HRrest and tachycardia, as well as decreased blood pressure and hypotension. Anthracyclines, trastuzumab, and left-sided radiation were associated with HRrest elevations and impairments of HRrecovery, but exercise training at least twice a week appeared to mitigate these changes. IMPLICATIONS FOR PRACTICE: This study characterized changes in clinically accessible measures with well-established prognostic value for cardiovascular disease, and investigated associations with cardiotoxic treatments and the positive influence of exercise. The chemotherapy-related incremental increase in resting heart rate, with tachycardia occurring in one third of patients, and decrease in blood pressure, with hypotension occurring in one half of the patients, is relevant to oncology practitioners for clinical examination or patient report of related symptoms (i.e., dizziness). The weekly dose of two 60-minute sessions of moderate-intensity aerobic and resistance exercise that was identified as protective of cardiovascular autonomic impairments can easily be prescribed to patients by oncologists.

Measurement and correction of the bulk magnetic susceptibility effects of fat: application in venous oxygen saturation imaging.

PURPOSE: To develop a correction method for the effects of the magnetic susceptibility of fat (χFat ) on the calculation of venous oxygen saturation (SvO2 ). THEORY: The magnetic field shifts associated with the magnetic susceptibility of deoxyhemoglobin can be used to estimate SvO2 , a measure of oxygen extraction and metabolism. However, the distinct magnetic susceptibility of fat surrounding targeted veins will give rise to magnetic field perturbations that will extend into the vein and surrounding tissues, potentially confounding the calculation of SvO2 . METHODS: Multi-echo modified Dixon fat-water separated imaging was used to quantify fat-water distributions around the superficial femoral vein (venous return from the lower leg). Fat fraction images were used to generate χFat images, to calculate and remove the associated fat-susceptibility-induced magnetic field shifts before the estimation of SvO2 . This approach was evaluated at rest and with plantar flexion exercise to evaluate calf muscle oxygen extraction in 10 healthy subjects. RESULTS: The presence of fat around the vein resulted in complex magnetic field shifts and errors in estimated SvO2 . Corrected resting SvO2 values were significantly larger than those measured with conventional methods, at rest (72.6 ± 11.0% vs. 65.2 ± 12.2%, P < 0.05) and post-exercise (37.4 ± 12.3% vs. 31.7 ± 12.7%, P < 0.05), with larger errors in individuals and/or regions with increased fat volumes. Estimation and removal of the field-effects from χFat enabled the use of fat tissues for the measurement and removal of the background magnetic field. CONCLUSIONS: The magnetic susceptibility effects of fat can confound SvO2 estimation, but the susceptibility field effects can estimated and removed with the use of modified Dixon fat-water separated imaging.

Correction to: Rationale and design of the Caloric Restriction and Exercise protection from Anthracycline Toxic Effects (CREATE) study: a 3-arm parallel group phase II randomized controlled trial in early breast cancer.

Following publication of the original article [1], we have been notified that one of the author names was listed incorrectly.

Maintenance of Fitness and Quality-of-Life Benefits From Supervised Exercise Offered as Supportive Care for Breast Cancer.

BACKGROUND: Overwhelming randomized controlled trial evidence demonstrates that exercise has positive health impacts during and after treatment for breast cancer. Yet, evidence generated by studies in which exercise programs are delivered outside a tightly controlled randomized trial setting is limited. The purpose of this study was to assess the effectiveness of an evidence-based exercise program with real-world implementation on physical fitness and quality of life (QoL). PATIENTS AND METHODS: Oncologists referred women with early-stage breast cancer who were scheduled to receive adjuvant chemotherapy. The program consisted of supervised aerobic and resistance exercise of moderate to vigorous intensity 3 times per week until the end of treatment (chemotherapy ± radiotherapy), then twice per week for 10 weeks, followed by once per week for 10 weeks. Health-related physical fitness and QoL were assessed at baseline, end of treatment, end of program, and 1-year follow-up. RESULTS: A total of 73 women were enrolled. Estimated peak VO2 (VO2peak), QoL, and body weight were maintained between baseline and end of treatment, whereas muscular strength improved (P<.01). By the end of the program, VO2peak, heart rate recovery, waist circumference, and some aspects of QoL were improved (all P<.01) relative to baseline. One year later, VO2peak, QoL, and waist circumference were maintained relative to end of program, whereas the improvements in strength and heart rate recovery had dissipated (all P<.01). CONCLUSIONS: Evidence-based exercise programming delivered with real-world implementation maintained VO2peak, strength, and QoL during adjuvant treatment and improved these measures after treatment completion among women with breast cancer. Continued guidance and support may be required for long-term maintenance of strength improvements in this population.

Effectiveness of Oncologist-Referred Exercise and Healthy Eating Programming as a Part of Supportive Adjuvant Care for Early Breast Cancer.

BACKGROUND: Randomized trials have established efficacy of supervised exercise training during chemotherapy for breast cancer for numerous health outcomes. The purpose of this study was to assess reach, effectiveness, maintenance, and implementation of an evidence-based exercise and healthy eating program offered within an adjuvant care setting. SUBJECTS, MATERIALS, AND METHODS: Women receiving adjuvant chemotherapy for breast cancer were given a prescription by their oncologist to participate in the Nutrition and Exercise during Adjuvant Treatment (NExT) program. The NExT program consisted of supervised, moderate-intensity, aerobic and resistance exercise three times a week during adjuvant therapy, followed by a step-down in supervised sessions per week for 20 additional weeks, plus one group-based healthy eating session. Usual moderate-to-vigorous physical activity (MVPA) and health-related quality of life (HRQoL) were assessed by questionnaire at baseline, program completion, and one year later, along with measures of satisfaction and safety. RESULTS: Program reach encompassed referral of 53% of eligible patients, 78% uptake (n = 73 enrolled), and 78% retention for the 45.0 ± 8.3-week program. During the program, MVPA increased (116 ± 14 to 154 ± 14 minutes per week, p = .014) and HRQoL did not change. One year later, MVPA (171 ± 24 minutes per week, p = .014) and HRQoL (44 ± 1 to 49 ± 1, p < .001) were significantly higher than baseline. Exercise adherence was 60% ± 26% to three sessions per week during treatment. No major adverse events occurred and injury prevalence did not change relative to baseline. Participants were highly satisfied. CONCLUSION: This oncologist-referred exercise and healthy eating supportive-care program for breast cancer patients receiving chemotherapy was safe, successful in reaching oncologists and patients, and effective for improving MVPA and maintaining HRQoL. IMPLICATIONS FOR PRACTICE: Despite evidence that exercise is both safe and efficacious at improving physical fitness, quality of life, and treatment side effects for individuals with cancer, lifestyle programming is not offered as standard of cancer care. This study describes an oncologist-referred, evidence-based exercise and healthy eating program offered in collaboration with a university as supportive care to women with breast cancer receiving chemotherapy. The program was well received by oncologists and patients, safe, and relatively inexpensive to operate. Importantly, there was a significant positive impact on physical activity levels and health-related quality of life lasting for 2 years after initiation of therapy.

The effect of an aerobic exercise bout 24 h prior to each doxorubicin treatment for breast cancer on markers of cardiotoxicity and treatment symptoms: a RCT.

PURPOSE: In rodents, a single exercise bout performed 24 h prior to a single doxorubicin treatment provides cardio-protection. This study investigated whether performing this intervention prior to every doxorubicin treatment for breast cancer reduced subclinical cardiotoxicity and treatment symptoms. METHODS: Twenty-four women with early stage breast cancer were randomly assigned to perform a 30-min, vigorous-intensity treadmill bout 24 h prior to each of four doxorubicin-containing chemotherapy treatments or to usual care. Established echocardiographic and circulating biomarkers of subclinical cardiotoxicity, as well as blood pressure and body weight were measured before the first and 7-14 days after the last treatment. The Rotterdam symptom checklist was used to assess patient-reported symptoms. RESULTS: The exercise and usual care groups did not differ in the doxorubicin-related change in longitudinal strain, twist, or cardiac troponin. However, the four total exercise bouts prevented changes in hemodynamics (increased cardiac output, resting heart rate, decreased systemic vascular resistance, p < 0.01) and reduced body weight gain, prevalence of depressed mood, sore muscles, and low back pain after the last treatment (p < 0.05) relative to the usual care group. No adverse events occurred. CONCLUSIONS: An exercise bout performed 24 h prior to every doxorubicin treatment did not have an effect on markers of subclinical cardiotoxicity, but had a positive systemic effect on hemodynamics, musculoskeletal symptoms, mood, and body weight in women with breast cancer. A single exercise bout prior to chemotherapy treatments may be a simple clinical modality to reduce symptoms and weight gain among women with breast cancer.

Rationale and design of the Caloric Restriction and Exercise protection from Anthracycline Toxic Effects (CREATE) study: a 3-arm parallel group phase II randomized controlled trial in early breast cancer.

BACKGROUND: Anthracycline chemotherapy agents are commonly used to treat breast cancer, but also result in cardiac injury, and potentially detrimental effects to vascular and skeletal muscle. Preclinical evidence demonstrates that exercise and caloric restriction can independently reduce anthracycline-related injury to the heart as well as cancer progression, and may be promising short-term strategies prior to treatment administration. For women with breast cancer, a short-term strategy may be more feasible and appealing, as maintaining regular exercise training or a diet throughout chemotherapy can be challenging due to treatment symptoms and psychosocial distress. METHODS: The Caloric Restriction and Exercise protection from Anthracycline Toxic Effects (CREATE) study will determine whether acute application of these interventions shortly prior to receipt of each treatment can reduce anthracycline-related toxicity to the heart, aorta, and skeletal muscle. Fifty-six women with early stage breast cancer scheduled to receive anthracycline treatment will be randomly assigned to one of three groups who will: 1) perform a single, 30-min, vigorous-intensity, aerobic exercise session 24 h prior to each anthracycline treatment; 2) consume a prepared diet reduced to 50% of caloric needs for 48 h prior to each anthracycline treatment; or 3) receive usual cancer care. The primary outcome is magnetic resonance imaging (MRI) derived left ventricular ejection fraction reserve (peak exercise LVEF - resting LVEF) at the end of anthracycline treatment. Secondary outcomes include MRI-derived measures of cardiac, aortic and skeletal muscle structure and function, circulating NT-proBNP, cardiorespiratory fitness and treatment symptoms. Exploratory outcomes include quality of life, fatigue, tumor size (only in neoadjuvant patients), oxidative stress and antioxidants, as well as clinical cardiac or cancer outcomes. MRI, exercise tests, and questionnaires will be administered before, 2-3 weeks after the last anthracycline treatment, and one-year follow-up. DISCUSSION: The proposed lifestyle interventions are accessible, low cost, drug-free potential methods for mitigating anthracycline-related toxicity. Reduced toxic effects on the heart, aorta and muscle are very likely to translate to short and long-term cardiovascular health benefits, including enhanced resilience to the effects of subsequent cancer treatment (e.g., radiation, trastuzumab) aging, and infection. TRIAL REGISTRATION: ClinicalTrials.gov NCT03131024; 4/21/18.

Predictors of attendance to an oncologist-referred exercise program for women with breast cancer.

PURPOSE: While exercise is associated with numerous benefits in women with breast cancer, adherence to exercise training concurrent to cancer treatment is challenging. We aimed to identify predictors of attendance to an oncologist-referred exercise program offered during and after adjuvant breast cancer treatment. METHODS: Women with early-stage breast cancer receiving chemotherapy (n = 68) enrolled in the Nutrition and Exercise During Adjuvant Treatment (NExT) study. Supervised aerobic and resistance exercise was prescribed three times per week during treatment, then one to two times per week for 20 additional weeks. Predictors of attendance were identified using multivariate linear regression for three phases of the intervention, including during (1) adjuvant chemotherapy, (2) radiation, and (3) 20-weeks post-treatment. RESULTS: Higher baseline quality of life (QoL) predicted higher attendance during chemotherapy (ß = 0.51%, 95 CI: 0.09, 0.93) and radiation (ß = 0.85%, 95 CI: 0.28, 1.41), and higher QoL, measured at the end of treatment, predicted higher attendance post-treatment (ß = 0.81%, 95 CI: 0.34, 1.28). Being employed pre-treatment (ß = 34.08%, 95 CI: 5.71, 62.45) and a personal annual income > $80,000 (ß = 32.70%, 95 CI: 0.85, 64.55) predicted higher attendance during radiation. Being divorced, separated or widowed (ß = - 34.62%, 95 CI: - 56.33, - 12.90), or single (ß = - 25.38%, 95 CI: - 40.64, - 10.13), relative to being married/common-law, and undergoing a second surgery (ß = - 21.37%, 95 CI: - 33.10, - 9.65) predicted lower attendance post-treatment. CONCLUSIONS: Demographic variables, QoL, and receipt of a second surgery significantly predicted attendance throughout the NExT supervised exercise program. These results may help identify individuals with exercise adherence challenges and improve the design of future interventions, including optimizing the timing of program delivery.

Effective Translation of Research to Practice: Hospital-Based Rehabilitation Program Improves Health-Related Physical Fitness and Quality of Life of Cancer Survivors.

BACKGROUND: Although exercise has been widely established as an efficacious rehabilitative therapy for cancer survivors in rigorously designed research studies, demonstration of translation of this research into clinical oncology practice is needed. The purpose of this study was to evaluate the effectiveness of a real-world cancer rehabilitation program implemented within a healthcare setting. PATIENTS AND METHODS: This study involved 299 adult cancer survivors enrolled in a hospital-based, supervised, individualized, cancer rehabilitation program. A retrospective review of the 132 participants who completed the follow-up assessment was performed. Sixty-minute sessions consisting of aerobic, resistance, flexibility, and relaxation exercises were performed twice weekly. Questionnaires and fitness assessments were administered at enrollment and after 24 sessions by exercise physiologists. Change in a number of health-related physical fitness and patient-reported outcomes and the influence of baseline characteristics on program outcomes were assessed. RESULTS: There were no baseline differences between those who completed the follow-up assessment and those who withdrew. Statistically and/or clinically meaningful improvements occurred in functional capacity, blood pressure, muscular endurance, flexibility, health-related quality of life, and fatigue, but not in body composition. Age, marital status, radiation treatment status, exercise frequency before diagnosis, smoking status, and alcohol consumption frequency influenced functional capacity and/or quality-of-life changes. CONCLUSIONS: Adoption of cancer rehabilitation as a standard part of oncology care may improve cancer survivors' health and well-being.