Evaluating predictive equations for energy requirements throughout breast cancer trajectory: A comparative study.

BACKGROUND & AIMS: Accurately estimating resting energy requirements is crucial for optimizing energy intake, particularly in the context of patients with varying energy needs, such as individuals with cancer. We sought to evaluate the agreement between resting energy expenditure (REE) predicted by 40 equations and that measured by reference methods in women undergoing active breast cancer treatment stage (I-IV) and post-completion (i.e., survivors). METHODS: Data from 4 studies were combined. REE values estimated from 40 predictive equations identified by a systematic search were compared with REE assessed by indirect calorimetry (IC) using a metabolic cart (MC-REE N = 46) or a whole-room indirect calorimeter (WRIC-REE N = 44). Agreement between methods was evaluated using Bland-Altman and Lin's concordance coefficient correlation (Lin's CCC). RESULTS: Ninety participants (24 % survivors, 61.1% had early-stage breast cancer I or II, mean age: 56.8 ± 11 years; body mass index: 28.7 ± 6.4 kg/m2) were included in this analysis. Mean MC-REE and WRIC-REE values were 1389 ± 199 kcal/day and 1506 ± 247 kcal/day, respectively. Limits of agreement were wide for all equations compared to both MC and WRIC (∼300 kcal for both methods), including the most commonly used ones, such as Harris-Benedict and Mifflin ST. Jeor equations; none had a bias within ±10% of measured REE, and all had low agreement per Lin's CCC analysis (<0.90). The Korth equation exhibited the best performance against WRIC and the Lvingston-Kohlstadt equation against MC. Similar patterns of bias were observed between survivors and patients and between patients with stages I-III versus IV cancer. CONCLUSION: Most equations failed to accurately predict REE at the group level, and none were effective at the individual level. This inaccuracy has significant implications for women with or surviving breast cancer, who may experience weight gain, maintenance, or loss due to inaccurate energy needs estimations. Therefore, our research underscores the need for further efforts to improve REE estimation.

Determinants of Impaired Peak Oxygen Uptake in Breast Cancer Survivors: JACC: CardioOncology Primer.

•Exercise intolerance is common among breast cancer survivors.•Exercise intolerance in breast cancer survivors is related to cardiac, vascular, and skeletal muscle impairments.•Holistic rehabilitation or pharmacological therapies are needed to address these impairments.

Determining the destination: a co-designed chronic advanced cancer rehabilitation conceptual framework for engagement of individuals with lived experience in rehabilitation research.

BACKGROUND: Individuals living with chronic advanced cancer (CAC) often face distinct physical, functional, and cognitive issues. Their rehabilitation needs are not yet routinely met, warranting further CAC-specific rehabilitation-based research. Given the complexity of functional and symptom presentations, engagement of individuals living with CAC as partners in the research process is encouraged to better understand the lived perspective. Formal engagement requires both structured approaches and iterative processes. The aim was to co-design a conceptual framework to develop and integrate engagement strategies into rehabilitation research focused on CAC populations. METHODS: A multidisciplinary team of authors, including two individuals with lived experience, conducted an implementation-focused descriptive study to inform future research design, including: interviews and follow-up, review of current models and approaches, and development of a co-designed conceptual framework for engaging individuals with lived experience into CAC-specific rehabilitation research. RESULTS: Emergent themes include shared understanding, transparent appreciation, iterative processes and unique partnership needs. A definition, guiding principles and tools for engagement were identified. In consultation with individuals with lived experience, and application of the emergent themes in context, a conceptual framework to guide the engagement process was developed. CONCLUSION: A novel conceptual framework for engaging individuals with lived experience with CAC as partners in rehabilitation research is proposed to facilitate implementation-focused team-based approaches for this population.

Living with chronic advanced cancer (CAC) affects all parts of a person's life. Rehabilitation, such as physiotherapy, can be necessary. Healthcare data shows that rehabilitation needs of people with CAC are not yet being regularly met and that more research in this area is needed. Because CAC is complex and impacts each person differently, having people with CAC included as partners on the research team will likely help researchers better understand and explain rehabilitation needs of people with CAC.Our group of authors include different healthcare professionals, researchers, and two individuals with lived experience. Together, we carried out an implementation study and designed a framework to guide other researchers in including individuals living with CAC on research teams.We found that important themes for individuals with lived experience were: shared understanding, transparent appreciation, iterative processes (such as back and forth communication) and unique partnership needs.We titled the conceptual framework a "Co-designed Chronic ADVanced CANCer Rehabilitation" or "Co-ADVANCE" for short.

Control4Life: A randomized controlled trial protocol examining the feasibility and efficacy of a combined pelvic health rehabilitation and exercise fitness program for individuals undergoing prostatectomy.

BACKGROUND: Urinary incontinence (UI), erectile dysfunction and cardiometabolic conditions are common after prostatectomy for prostate cancer (PCa). Although physical activity could improve overall survival and quality of survivorship, fear of UI can restrict participation in exercise. Individuals with PCa could benefit from therapeutic exercise programming to support continence recovery and cardiometabolic health. AIM: The main objective of this study is to determine the feasibility and the effects of a combined pelvic health rehabilitation and exercise fitness program on UI after prostatectomy. The combined exercise program will be delivered both in-person and virtually. METHODS: This study follows a modified Zelen, two-arm parallel randomized controlled trial design. A total of 106 individuals with PCa will be recruited before prostatectomy surgery. Participants will be randomized between two groups: one receiving usual care and one receiving a combined exercise fitness and intensive pelvic floor muscle training program. Exercise programming will begin 6-8 weeks after prostatectomy and will last 12 weeks. Outcomes include: the 24-h pad test (primary outcome for UI); physical fitness, metabolic indicators, and patient-reported outcomes on erectile function, self-efficacy, severity of cancer symptoms and quality of life. Important timepoints for assessments include before surgery (T0), after surgery (T1), after intervention (T3) and at one-year after surgery (T4). CONCLUSION: This study will inform the feasibility of offering comprehensive exercise programming that has the potential to positively impact urinary continence, erectile function and cardiometabolic health of individuals undergoing prostatectomy for prostate cancer. CLINICALTRIALS REGISTRATION NUMBER: NCT06072911.

A Review on the Role of Exercise Training to Prevent a Decline in Cardiorespiratory Fitness and Cardiac Function in Breast Cancer Survivors.

PURPOSE: Improvements in diagnosis and treatment mean that the long-term health of breast cancer survivors (BCS) is increasingly dictated by cardiovascular comorbidities. This is partly a consequence of exposure to cardiotoxic therapies, which result in cardiac dysfunction and decreased cardiorespiratory fitness (CRF). Exercise training (ExT) is a key therapeutic strategy for secondary prevention and increasing CRF in adults with established cardiovascular disease. Exercise-based cardio-oncology rehabilitation (CORE) has been proposed as an emerging strategy to address CRF and cardiac impairment in BCS. This review aims to (1) provide an overview of the impact of breast cancer therapy on CRF; (2) provide an up-to-date summary of the effects of ExT on CRF and cardiac function in BCS undergoing cardiotoxic therapy; and (3) discuss how traditional ExT approaches can be adapted for BCS undergoing therapy. REVIEW METHODS: A literature review was performed based on an intensive literature search for systematic reviews and meta-analyses, randomized and non-randomized controlled trials and single-arm trials investigating the impact of exercise training or cardiac rehabilitation on CRF and/or cardiac function in BCS who are undergoing or have completed cardiotoxic cancer therapy. SUMMARY: Overall, current evidence suggests that ExT induces clinically meaningful benefits for CRF in BCS during and after therapy. There is also emerging evidence that ExT can improve peak exercise measures of cardiac function; however, there is a need for further research to understand how to adapt these effective ExT approaches into clinical CORE-based settings.

Endothelin Receptor Blocker Reverses Breast Cancer-Induced Cardiac Remodeling.

Background: Although some cancer therapies have overt and/or subclinical cardiotoxic effects that increase subsequent cardiovascular risk in breast cancer patients, we have recently shown that the breast tumor itself can also induce cardiac hypertrophy through the activation of the endothelin system to contribute to cardiovascular risk. However, the extent to which the suppression of the activation of the endothelin system could improve cardiac remodeling in breast cancer patients has yet to be investigated. Objectives: We aimed to retrospectively assess the cardiac morphology/function in patients with breast cancer before receiving cancer chemotherapy and to investigate if the suppression of the activation of the endothelin system improves cardiac remodeling in a mouse model of breast cancer. Methods: Our study involved 28 previously studied women with breast cancer (including 24 after tumor resection) before receiving adjuvant therapy and 17 control healthy women. In addition, we explored how the endothelin system contributed to breast cancer-induced cardiac remodeling using a mouse model of breast cancer. Results: Our results indicate that before chemotherapy, breast cancer patients already exhibit relative cardiac remodeling and subclinical cardiac dysfunction, which was associated with the activation of the endothelin system. Importantly, our mouse data also show that the endothelin receptor blocker atrasentan significantly lessened cardiac remodeling and improved cardiac function in a preclinical model of breast cancer. Conclusions: Although our findings should be further examined in other preclinical/clinical models, our data suggest that endothelin receptor blockers may play a role in cardiac health in individuals with breast cancer. (Understanding and Treating Heart Failure With Preserved Ejection Fraction: Novel Mechanisms, Diagnostics and Potential Therapeutics [Alberta HEART]; NCT02052804 and Multidisciplinary Team Intervention in Cardio-Oncology [TITAN]; NCT01621659).

Cardio-oncology and Cancer Rehabilitation: Is an Integrated Approach Possible?

With significant improvements in the understanding of cancer biology, improved detection, and the use of novel adjuvant therapies, each year more Canadians are surviving a cancer diagnosis. Despite their effectiveness these therapies often result in short- and long-term deleterious effects to major organ systems, particularly cardiovascular. Cardio-oncology is an emerging field of study with the aim to improve cardiovascular health across the oncology disease spectrum. International guidelines distinguish "cardio-oncology" rehabilitation from "cancer" rehabilitation, but how this is navigated is currently unknown. How such care should be assessed and integrated acutely or in the longer term remains unknown. Accordingly, the aim of this article is to consider the cancer patient's needs beyond the scope of cardio-oncology rehabilitation to holistically integrate cancer rehabilitation across the disease trajectory.

Does cardiac imaging surveillance strategy influence outcomes in patients with early breast cancer?

Background: Many patients with breast cancer receive therapies with the potential to cause cardiotoxicity. Echocardiography and multiple-gated acquisition (MUGA) scans are the most used modalities to assess cardiac function during treatment in high-risk patients; however, the optimal imaging strategy and the impact on outcome are unknown. Methods: Consecutive patients with stage 0-3 breast cancer undergoing pre-treatment echocardiography or MUGA were identified from a tertiary care cancer center from 2010-2019. Demographics, medical history, imaging data and clinical events were collected from hospital charts and administrative databases. The primary outcome is a composite of all-cause death or heart failure event. Clinical and imaging predictors of outcome were evaluated on univariable and multivariable analyses. Results: 1028 patients underwent pre-treatment MUGA and 1032 underwent echocardiography. The groups were well matched for most clinical characteristics except patients undergoing MUGA were younger, had more stage 3 breast cancer and more HER2 over-expressing and triple negative cases. Routine follow-up cardiac imaging scan was obtained in 39.3% of patients with MUGA and 38.0% with echocardiography. During a median follow-up of 2448 (1489, 3160) days, there were 194 deaths, including 7 cardiovascular deaths, and 28 heart failure events with no difference in events between the MUGA and echocardiography groups. There were no imaging predictors of the primary composite outcome or cardiac events. Patients without follow-up imaging had similar adjusted risk for the composite outcome compared to those with imaging follow-up, hazard ratio 0.8 (95% confidence interval 0.5,1.3), p=0.457. Conclusion: The selection of pretreatment echocardiography or MUGA did not influence the risk of death or heart failure in patients with early breast cancer. Many patients did not have any follow-up cardiac imaging and did not suffer worse outcomes. Cardiovascular deaths and heart failure event rates were low and the value of long-term cardiac imaging surveillance should be further evaluated.

Phase angle is associated with muscle health and cardiorespiratory fitness in older breast cancer survivors.

BACKGROUND & AIM: Phase angle (PhA) obtained from bioelectrical impedance analysis (BIA) is an indicator of cellular integrity and relates to several chronic conditions. The purpose of this secondary analysis was to evaluate the association of PhA with health-related physical fitness, namely, cardiorespiratory fitness, skeletal muscle volume, and myosteatosis (i.e. muscle health) in older breast cancer survivors. METHODS: Twenty-two women ≥60 years with a body mass index (BMI) ≥25 kg/m2 and who completed chemotherapy for early-stage breast cancer were included. BIA, cardiopulmonary exercise tests and magnetic resonance imaging scans were completed before and after eight weeks of time-restricted eating. RESULTS: At baseline, PhA was associated with cardiorespiratory fitness (R2 = 0.54, p < 0.01) and skeletal muscle volume (R2 = 0.83, p < 0.01) and myosteatosis (R2 = 0.25, p = 0.02). Results were similar at follow-up. CONCLUSION: Findings from this pilot study suggest that higher values of PhA are associated with better health-related physical fitness among older breast cancer survivors.

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.

Exercise Preferences, Barriers, and Facilitators of Individuals With Cancer Undergoing Chemotherapy Before Stem Cell Transplantation: A Mixed-Methods Study.

BACKGROUND: Exercise can help mitigate side effects of hematopoietic stem cell transplantation (HSCT), particularly when initiated before HSCT. However, the exercise-related barriers, facilitators, and preferences of this population remain unclear. OBJECTIVE: This study aimed to explore the patient experience to inform future implementation of a prehabilitation intervention. INTERVENTIONS/METHODS: A 2-phase sequential explanatory mixed-methods study was conducted using (1) cross-sectional survey and (2) focus groups. Survey questions aligned with the Theoretical Domains Framework. Focus group data were analyzed using a directed content analysis approach, followed by inductive thematic analysis to generate themes that represented the exercise-related barriers, facilitators, and preferences of participants. RESULTS: Twenty-six participants completed phase 1 (n = 22 with multiple myeloma). Fifty percent of participants (n = 13) were fairly/very confident in their ability to exercise pre-HSCT. Eleven participants completed phase 2. Exercise barriers included knowledge/skill limitations, inadequate healthcare provider support, and the emotional toll of treatment. Facilitators included social support and goals. Exercise preferences were related to 2 themes: (1) program structure (subthemes: prescription and scheduling, mode of delivery) and (2) support (subthemes: support from personnel, tailoring, and education). CONCLUSION: Key exercise-related barriers included knowledge limitations, disease/treatment effects, and inadequate support. Prehabilitation should be tailored, flexible, and include education and a virtual or hybrid delivery model in this population. IMPLICATIONS FOR PRACTICE: Nurses are well positioned to identify functional limitations and counsel and refer patients to exercise programming and/or physiotherapy services. Including an exercise professional in the pretransplant care team would provide key supportive care assistance for the nursing team.

Implementation of weekday time-restricted eating to improve metabolic health in breast cancer survivors with overweight/obesity.

OBJECTIVE: This study aimed to evaluate the implementation of telephone-based delivery of weekday-only time-restricted eating (TRE), its preliminary efficacy for metabolic outcomes, and concurrent lifestyle changes. METHODS: Twenty-two breast cancer survivors aged 60+ years with overweight/obesity completed an 8-week feasibility study of 12 to 8 p.m. weekday-only ad libitum TRE. The intervention was delivered by one registered dietitian call, twice-daily automated text messages asking about eating start and stop times, and three support phone calls. Magnetic resonance imaging, venipuncture, and 3 days of diet records and accelerometry were performed at baseline and after intervention. RESULTS: Participants had a mean age of 66 (SD 5) years with BMI of 31.8 (4.8) kg/m2 . Intervention implementation was successful, including excellent adherence (98%), participant acceptability, and a low symptom profile and cost ($63/participant). There were no significant changes in individual components of metabolic syndrome, lipid profile, or hemoglobin A1c , despite clinically relevant changes occurring within individual participants. Magnetic resonance imaging-derived hepatic steatosis and thigh myosteatosis did not change. Dietary intake changes included reduced energy (-22%) and protein (-0.2 g/kg). Physical activity and sleep did not change. CONCLUSIONS: Eight weeks of telephone-delivered weekday TRE is a feasible, acceptable, low-symptom, and low-cost intervention. Future studies may consider a longer intervention length for more consistent metabolic improvements and counseling to enhance protein intake.

Rationale and design of IMPACT-women: a randomised controlled trial of the effect of time-restricted eating, healthy eating and reduced sedentary behaviour on metabolic health during chemotherapy for early-stage breast cancer.

Metabolic dysfunction and excess accumulation of adipose tissue are detrimental side effects from breast cancer treatment. Diet and physical activity are important treatments for metabolic abnormalities, yet patient compliance can be challenging during chemotherapy treatment. Time-restricted eating (TRE) is a feasible dietary pattern where eating is restricted to 8 h/d with water-only fasting for the remaining 16 h. The purpose of this study is to evaluate the effect of a multimodal intervention consisting of TRE, healthy eating, and reduced sedentary time during chemotherapy treatment for early-stage (I-III) breast cancer on accumulation of visceral fat (primary outcome), other fat deposition locations, metabolic syndrome and cardiovascular disease risk (secondary outcomes) compared with usual care. The study will be a two-site, two-arm, parallel-group superiority randomised control trial enrolling 130 women scheduled for chemotherapy for early-stage breast cancer. The intervention will be delivered by telephone, including 30-60-minute calls with a registered dietitian who will provide instructions on TRE, education and counselling on healthy eating, and goal setting for reducing sedentary time. The comparison group will receive usual cancer and supportive care including a single group-based nutrition class and healthy eating and physical activity guidelines. MRI, blood draws and assessment of blood pressure will be performed at baseline, after chemotherapy (primary end point), and 2-year follow-up. If our intervention is successful in attenuating the effect of chemotherapy on visceral fat accumulation and cardiometabolic dysfunction, it has the potential to reduce risk of cardiometabolic disease and related mortality among breast cancer survivors.

TITAN Trial: A Randomized Controlled Trial of a Cardiac Rehabilitation Care Model in Breast Cancer.

Background: Cardiac rehabilitation (CR) modeled care is recommended for patients with breast cancer to mitigate risk of cardiotoxicity. However, the cardiovascular impact of CR-modeled interventions has not been studied. Objectives: The purpose of this study was to evaluate if a multidisciplinary model of CR reduces cardiotoxicity and improves cardiovascular risk in patients undergoing breast cancer treatment. Methods: We randomly assigned patients with stage I to III breast cancer scheduled to receive anthracycline and/or trastuzumab-based chemotherapy to the CR intervention (n = 37) or usual care (n = 37). The intervention included guideline-directed management of cardiovascular risk factors, dietary counselling, and supervised exercise for 52 weeks. Cardiac magnetic resonance imaging, cardiopulmonary exercise testing, dual-energy x-ray absorptiometry, and serum biomarkers were acquired at baseline and 52 weeks. Results: There was no difference in the primary outcome, left ventricular ejection fraction (LVEF), between groups at 52 weeks (61% ± 6%). Other markers of cardiotoxicity, including high-sensitivity troponin I and brain natriuretic peptide, were similar between groups. However, total cholesterol (5.2 ± 0.8 mmol/L to 4.7 ± 0.8 mmol/L, P = 0.002) and low-density lipoprotein (3.0 ± 0.7 mmol/L to 2.4 ± 0.7 mmol/L, P < 0.001) decreased in the intervention group at 52 weeks and were unchanged in usual care. In all patients, adverse cardiac and metabolic changes occurred over 52 weeks including reductions in LVEF, left ventricular mass, high-density lipoprotein, lean body mass, insulin-like growth factor-1, as well as increased triglycerides, whole-body and truncal fat mass (all P < 0.050). Conclusions: The CR-modeled intervention had no effect on LVEF or biomarkers of cardiotoxicity. Future lifestyle intervention trials in patients with breast cancer should consider targeting other risk factors associated with incident cardiovascular disease. (Multidisciplinary Team IntervenTion in CArdio-ONcology [TITAN Study] [TITAN]; NCT01621659).

Determinants of oxygen utilization in breast cancer: Similarities between heart failure with preserved ejection fraction.

Reduced exercise tolerance and fatigue are hallmark features in both breast cancer (BC) and heart failure with preserved ejection fraction (HFpEF) and are associated with decreased physical function and quality of life. This brief review focuses on the mechanisms of exercise intolerance in women with BC across the survivorship continuum and highlights how these disturbances within the oxygen transport cascade are similar to that of HFpEF patients. Specifically, the role that impaired cardiac, peripheral vascular and skeletal muscle function play in limiting peak oxygen uptake are discussed. We propose that women with BC are at increased risk of developing HFpEF potentially due to the adverse effects of chemotherapy and concurrent adverse lifestyle behaviors on cardiovascular and skeletal muscle function.

Virtual or In-Person: A Mixed Methods Survey to Determine Exercise Programming Preferences during COVID-19.

A survey was conducted to identify barriers and facilitators to engaging in virtual and in-person cancer-specific exercise during COVID-19. A theory-informed, multi-method, cross-sectional survey was electronically distributed to 192 individuals with cancer investigating preferences towards exercise programming during COVID-19. Respondents had previously participated in an exercise program and comprised two groups: those who had experience with virtual exercise programming ('Virtual') and those who had only taken part in in-person exercise ('In-Person'). Quantitative data were summarized descriptively. Qualitative data were thematically categorized using framework analysis and findings were mapped to an implementation model. The survey completion response rate was 66% (N = 127). All respondents identified barriers to attending in-person exercise programming during COVID-19 with concerns over the increased risk of viral exposure. Virtual respondents (n = 39) reported: (1) feeling confident in engaging in virtual exercise; and (2) enhanced motivation, accessibility and effectiveness as facilitators to virtual exercise. In-Person respondents (n = 88) identified: (1) technology as a barrier to virtual exercise; and (2) low motivation, accessibility and exercise effectiveness as barriers towards virtual exercise. Sixty-six percent (n = 58) of In-Person respondents reported that technology support would increase their willingness to exercise virtually. With appropriately targeted support, perceived barriers to accessing virtual exercise-including motivation, accessibility and effectiveness-may become facilitators. The availability of technology support may increase the engagement of individuals with cancer towards virtual exercise programming.

Feasibility of Implementing Cancer-Specific Community-Based Exercise Programming: A Multi-Centre Randomized Trial.

BACKGROUND: There is growing recognition of the importance of reporting preliminary work on the feasibility of a trial. The present study aimed to assess the feasibility of (1) a proposed fitness testing battery, and (2) processes related to the implementation of cancer-specific exercise programming in a community setting. METHODS/DESIGN: A randomized controlled implementation feasibility trial was performed in advance of a large-scale implementation study. Eligible participants within 18 months of a cancer diagnosis were randomized to immediate or delayed community-based exercise at YMCA locations in Calgary and Edmonton, Canada for an 8-week period. The primary outcome for the trial was the feasibility of the physical fitness testing battery, defined as a 70% or greater completion rate across the 24-week study period. The Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework was used to evaluate processes related to implementation of the exercise program across the two sites. RESULTS: Eighty participants were recruited, 73 (91%) completed the 8-week trial, and 68 (85%) completed the 16- and 24-week follow-ups. Sixty participants (75%) completed the full physical fitness test battery at each time point, and 59 (74%) completed the patient-reported outcome measures. Statistically significant between-group differences were found in favor of the exercise group for functional aerobic capacity, upper and lower extremity strength, and symptoms. Differences were found between the sites, however, in completion rates and processes related to program implementation. DISCUSSION: Findings suggest the need for minor adaptations to the physical fitness battery and outcome measures to better fit the community context. While findings support feasibility, context-specific challenges related to implementation processes were identified.