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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.

Anelloviruses are highly prevalent in diverse mammals, including humans, but so far have not been linked to any disease and are considered to be part of the ‘healthy virome’. These viruses have small circular single-stranded DNA (ssDNA) genomes and encode several proteins with no detectable sequence similarity to proteins of other known viruses. Thus, anelloviruses are the only family of eukaryotic ssDNA viruses currently not included in the realm Monodnaviria. To gain insights into the provenance of these enigmatic viruses, we sequenced more than 250 complete genomes of anelloviruses from nasal and vaginal swab samples of Weddell seal (Leptonychotes weddellii) from Antarctica and a fecal sample of grizzly bear (Ursus arctos horribilis) from USA, and performed a comprehensive family-wide analysis of the signature anellovirus protein, ORF1. Using state-of-the-art remote sequence similarity detection approaches and structural modeling with AlphaFold2, we show that ORF1 orthologs from all Anelloviridae genera adopt a jelly-roll fold typical of viral capsid proteins, establishing an evolutionary link to other eukaryotic ssDNA viruses, specifically, circoviruses. However, unlike capsid proteins of other ssDNA viruses, ORF1 encoded by anelloviruses from different genera display remarkable variation in size, due to insertions into the jelly-roll domain. In particular, the insertion between β-strands H and I forms a projection domain predicted to face away from the capsid surface and function at the interface of virus-host interactions. Consistent with this prediction and supported by recent experimental evidence, the outermost region of the projection domain is a mutational hotspot, where rapid evolution was likely precipitated by the host immune system. Collectively, our findings further expand the known diversity of anelloviruses and explain how anellovirus ORF1 proteins likely diverged from canonical jelly-roll capsid proteins through gradual augmentation of the projection domain. We suggest assigning Anelloviridae to a new phylum, ‘Commensaviricota’, and including it into kingdom Shotokuvirae (realm Monodnaviria), alongside Cressdnaviricota and Cossaviricota.

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.

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.

We systematically reviewed and synthesized evidence on the impact of physical activity/exercise on cancer treatment efficacy. We included six preclinical and seven clinical studies. Exercise significantly enhanced the efficacy of chemotherapy and tamoxifen in seven of eight rodent models in either an additive, sensitizing, or synergistic manner. In clinical studies, preliminary evidence indicates that exercise during neoadjuvant, primary, and adjuvant treatment may enhance efficacy of cancer therapies; however, no clinical study was designed for this purpose. Here we discuss the biological mechanisms of exercise-associated enhancement of therapeutic efficacy and propose future research directions to definitively examine the effects of exercise on cancer treatment and patient outcomes.

This study aimed to characterize peak exercise cardiac function and thigh muscle fatty infiltration and their relationships with VO2peak among anthracycline-treated breast cancer survivors (BCS). BCS who received anthracycline chemotherapy ~ 1 year earlier (n = 16) and matched controls (matched-CON, n = 16) were enrolled. Resting and peak exercise cardiac function, myocardial T1 mapping (marker of fibrosis), and thigh muscle fat infiltration were assessed by magnetic resonance imaging, and VO2peak by cycle test. Compared to matched-CON, BCS had lower peak SV (64 ± 9 vs 57 ± 10 mL/m2, p = 0.038), GLS (− 30.4 ± 2.2 vs − 28.0 ± 2.5%, p = 0.008), and arteriovenous oxygen difference (16.4 ± 3.6 vs 15.2 ± 3.9 mL/100 mL, p = 0.054). Mediation analysis showed: (1) greater myocardial T1 time (fibrosis) is inversely related to cardiac output and end-systolic volume exercise reserve; (2) greater thigh muscle fatty infiltration is inversely related to arteriovenous oxygen difference; both of which negatively influence VO2peak. Peak SV (R2 = 65%) and thigh muscle fat fraction (R2 = 68%) were similarly strong independent predictors of VO2peak in BCS and matched-CON combined. Post-anthracyclines, myocardial fibrosis is associated with impaired cardiac reserve, and thigh muscle fatty infiltration is associated with impaired oxygen extraction, which both contribute to VO2peak.

This commentary highlights the challenges of clinical trials, especially as related to trials on exercise for older adults with advanced cancer, and comments on the study by Mikkelsen et al.

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.

The profound impacts that maternal provisioning of finite energy resources has on offspring survival have been extensively studied across mammals. This study shows that in addition to calories, high hemoprotein concentrations in diving mammals necessitates exceptional female-to-pup iron transfer. Numerous indices of iron mobilization (ferritin, serum iron, total-iron-binding-capacity, transferrin saturation) were significantly elevated during lactation in adult female Weddell seals (Leptonychotes weddellii), but not in skip-breeders. Iron was mobilized from endogenous stores for incorporation into the Weddell seal’s milk at concentrations up to 100× higher than terrestrial mammals. Such high rates of iron offload to offspring drew from the female’s own heme stores and led to compromised physiologic dive capacities (hemoglobin, myoglobin, and total body oxygen stores) after weaning their pups, which was further reflected in shorter dive durations. We demonstrate that lactational iron transfer shapes physiologic dive thresholds, identifying a cost of reproduction to a marine mammal.

Summary Background & aims Preclinical evidence suggests that caloric restriction is an effective therapy for a number of cardiovascular insults. Whether caloric restriction has cardio-protective effects in humans is not well understood. The aim was to systematically review and meta-analyze human randomized control trials (RCTs) testing the effect of caloric restriction on blood pressure (BP) and cardiovascular function. Methods A systematic review was performed using Medline, EMBASE, CINAHL (up to June 2017) to search for RCTs of adults receiving a calorie-restricted intervention versus a control/standard diet. Random-effect meta-analyses were performed to calculate weighted mean difference and 95% CI. Results Thirty-two RCTs with 1722 participants assessing BP (n = 29 studies), heart rate (n = 10), VO2peak (n = 8), muscle sympathetic nerve activity (MSNA, n = 4), and endothelial function (n = 4) were included. Calorie-restricted interventions lasting 1–4 weeks had the largest effect on systolic (−5.5 mmHg, p Conclusions The effect of 1–4 weeks of calorie restriction on BP was similar to that expected with medications, and larger than that reported for other lifestyle interventions or supplements. Cardiovascular risk could be further reduced by caloric restriction lasting up to six months to lower heart rate and improve VO2peak.

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.

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. 31Phosphorus 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 (SvO2), 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, SvO2, 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.

There is substantial overlap in risk factors for the pathogenesis and progression of breast cancer (BC) and cardiovascular disease (CVD), including obesity, metabolic disturbances, and chronic inflammation. These unifying features remain prevalent after a BC diagnosis and are exacerbated by BC treatment, resulting in elevated CVD risk among survivors. Thus, therapies that target these risk factors or mechanisms are likely to be effective for the prevention or progression of both conditions. In this narrative review, we propose time-restricted eating (TRE) as a simple lifestyle therapy to address many upstream causative factors associated with both BC and CVD. TRE is simple dietary strategy that typically involves the consumption of ad libitum energy intake within 8 h, followed by a 16-h fast. We describe the feasibility and safety of TRE and the available evidence for the impact of TRE on metabolic, cardiovascular, and cancer-specific health benefits. We also highlight potential solutions for overcoming barriers to adoption and adherence and areas requiring future research. In composite, we make the case for the use of TRE as a novel, safe, and feasible intervention for primary and secondary BC prevention, as well as tertiary prevention as it relates to CVD in BC survivors.

Circoviridae is a family of circular single-stranded DNA viruses whose members infect a wide variety of hosts. While well characterized in avian and mammalian hosts, little is known about circoviruses associated with Antarctic animals. From 48 Weddell seal (Leptonychotes weddellii) fecal samples collected on the sea ice in McMurdo between Nov 2014 and Dec 2014, we identified and determined the genomes of novel viruses that fall within two genera of the family Circoviridae, i.e. Circovirus (n = 7) and Cyclovirus (n = 45). We named these viruses as werosea circovirus (WerCV) and werosea cyclovirus (WerCyV). The genomes of WerCV and WerCyV share ~63–64% genome-wide pairwise identity with classified circoviruses and cycloviruses, respectively. Based on the species demarcation threshold of 80% for members of the Circoviridae, the genomes of WerCV and WerCyV represent new species in their respective genera. Evidence indicated recombination in five of the 45 WerCyV genomes identified in this study. These are the first circoviruses found associated with Antarctic pinnipeds, adding to those recently identified associated with Adelie (Pygoscelis adeliae) and chinstrap penguins (P. antarcticus).

Exercise-based, multimodal rehabilitation programming similar to that used in the existing models of cardiac or pulmonary rehabilitation or prehabilitation is a holistic potential solution to address the range of physical, psychological, and existential (e.g., as their diagnosis relates to potential death) stressors associated with a cancer diagnosis and subsequent treatment. The purpose of this study was to systematically evaluate the structure and format of any type of exercise-based, multimodal rehabilitation programs used in individuals with cancer and the evidence base for their real-world effectiveness on metrics of physical (e.g., cardiorespiratory fitness, blood pressure) and psychological (e.g., health-related quality of life) health. Very few of the 33 included exercise-based, multimodal rehabilitation programs employed intervention components, education topics, and program support staff that were multi-disciplinary or cancer-specific. In particular, a greater emphasis on nutrition care, and the evaluation and management of psychosocial distress and CVD risk factors, with cancer-specific adaptations, would broaden and maximize the holistic health benefits of exercise-based rehabilitation. Despite these opportunities for improvement, exercise-based, multimodal rehabilitation programs utilized under real-world settings in individuals with cancer produced clinically meaningful and large effect sizes for cardiorespiratory fitness (VO2peak, ±2.9 mL/kg/min, 95% CI = 2.6 to 3.3) and 6-minute walk distance (+47 meters, 95% CI = 23 to 71), and medium effect sizes for various measures of cancer-specific, health-related quality of life. However, there were no changes to blood pressure, body mass index, or lung function. Overall, these findings suggest that exercise-based, multimodal rehabilitation is a real-world therapy that improves physical and psychological health among individuals with cancer, but the holistic health benefits of this intervention would likely be enhanced by addressing nutrition, psychosocial concerns, and risk factor management through education and counselling with consideration of the needs of an individual with cancer.

Exercise may improve fatigue in multiple myeloma survivors, but trial evidence is limited, and exercise may be perceived as risky in this older patient group with osteolytic bone destruction.In this Phase 2 Zelen trial, multiple myeloma survivors who had completed treatment at least 6 weeks ago, or were on maintenance only, were enrolled in a cohort study and randomly assigned to usual care or a 6-month exercise programme of tailored aerobic and resistance training. Outcome assessors and usual care participants were masked. The primary outcome was the FACIT-F fatigue score with higher scores denoting less fatigue.During 2014-2016, 131 participants were randomised 3:1 to intervention (n = 89) or usual care (n = 42) to allow for patients declining allocation to the exercise arm. There was no difference between groups in fatigue at 3 months (between-group mean difference: 1.6 [95% CI: -1.1-4.3]) or 6 months (0.3 [95% CI: -2.6-3.1]). Muscle strength improved at 3 months (8.4 kg [95% CI: 0.5-16.3]) and 6 months (10.8 kg [95% CI: 1.2-20.5]). Using per-protocol analysis, cardiovascular fitness improved at 3 months (+1.2 ml/kg/min [95% CI: 0.3-3.7]). In participants with clinical fatigue (n = 17), there was a trend towards less fatigue with exercise over 6 months (6.3 [95% CI: -0.6-13.3]). There were no serious adverse events.Exercise appeared safe and improved muscle strength and cardiovascular fitness, but benefits in fatigue appeared limited to participants with clinical fatigue at baseline. Future studies should focus on patients with clinical fatigue.The study was registered with ISRCTN (38480455) and is completed.

PURPOSE The purpose of this study was to provide a rationale for "chemotherapy-periodized" exercise by characterizing cyclical variations in fatigue and exercise response across a chemotherapy cycle and comparing exercise adherence during chemotherapy between a prescription that is periodized according to chemotherapy cycle length and a standard linearly progressed prescription. METHODS Women with breast cancer who were prescribed taxane-based chemotherapy were randomly assigned to a supervised aerobic and resistance exercise program after a chemotherapy-periodized exercise prescription (n = 12) or to usual care during chemotherapy (n = 15). Fatigue and steady state exercise responses were assessed in both groups before the first taxane treatment and across the third treatment (i.e., 0-3 d prior and 3-5 d after the third treatment, and 0-3 d before the fourth treatment) to assess cyclical variations. Adherence to the chemotherapy-periodized exercise prescription was compared with adherence to a standard linear prescription from a prior study in a similar population (n = 51). RESULTS Fatigue increased from baseline (marginal mean ± standard error: 3.2 ± 0.4) to before the third treatment (4.1 ± 0.4, P = 0.025), then peaked at 3 to 5 d after the third treatment (5.1 ± 0.4, P = 0.001), before recovering before the fourth treatment (4.3 ± 0.5, P = 0.021). The peak in fatigue at 3 to 5 d post-third treatment corresponded to a decrease in steady state exercise oxygen consumption (V˙O2) (P = 0.013). Compared with a standard linear exercise prescription during chemotherapy, a chemotherapy-periodized exercise prescription resulted in higher attendance during the week after chemotherapy (57% ± 30% vs 77% ± 28%, P = 0.04) and overall attendance (63% + 25% vs 78% ± 23%, P = 0.05). CONCLUSIONS Fatigue and exercise V˙O2 vary across a chemotherapy cycle. A chemotherapy-periodized exercise prescription that accommodates cyclical variations in fatigue may increase adherence to supervised exercise.

Seasonal resource pulses can have enormous impacts on species interactions. In marine ecosystems, air-breathing predators often drive their prey to deeper waters. However, it is unclear how ephemeral resource pulses such as near-surface phytoplankton blooms alter the vertical trade-off between predation avoidance and resource availability in consumers, and how these changes cascade to the diving behaviour of top predators. We integrated data on Weddell seal diving behaviour, diet stable isotopes, feeding success and mass gain to examine shifts in vertical foraging throughout ice break-out and the resulting phytoplankton bloom each year. We also tested hypotheses about the likely location of phytoplankton bloom origination (advected or producedin situwhere seals foraged) based on sea ice break-out phenology and advection rates from several locations within 150 km of the seal colony. In early summer, seals foraged at deeper depths resulting in lower feeding rates and mass gain. As sea ice extent decreased throughout the summer, seals foraged at shallower depths and benefited from more efficient energy intake. Changes in diving depth were not due to seasonal shifts in seal diets or horizontal space use and instead may reflect a change in the vertical distribution of prey. Correspondence between the timing of seal shallowing and the resource pulse was variable from year to year and could not be readily explained by our existing understanding of the ocean and ice dynamics. Phytoplankton advection occurred faster than ice break-out, and seal dive shallowing occurred substantially earlier than local break-out. While there remains much to be learned about the marine ecosystem, it appears that an increase in prey abundance and accessibility via shallower distributions during the resource pulse could synchronize life-history phenology across trophic levels in this high-latitude ecosystem.

Women have unique sex- and gender-related risk factors for cardiovascular disease (CVD) that can present or evolve over their lifespan. Pregnancy-associated conditions, polycystic ovarian syndrome, and menopause can increase a woman’s risk of CVD. Women are at greater risk for autoimmune rheumatic disorders, which play a role in the predisposition and pathogenesis of CVD. The influence of traditional CVD risk factors (eg, smoking, hypertension, diabetes, obesity, physical inactivity, depression, anxiety, and family history) is greater in women than men. Finally, there are sex differences in the response to treatments for CVD risk and comorbid disease processes. In this Atlas chapter we review sex- and gender-unique CVD risk factors that can occur across a woman’s lifespan, with the aim to reduce knowledge gaps and guide the development of optimal strategies for awareness and treatment. Résumé: Les femmes présentent des facteurs de risque de maladies cardiovasculaires (MCV) uniques, liés au sexe et au genre, qui peuvent se manifester ou évoluer tout au long de leur vie. Les troubles médicaux associés à la grossesse, le syndrome des ovaires polykystiques et la ménopause peuvent augmenter le risque de MCV chez une femme. Les femmes sont plus exposées aux troubles rhumatologiques auto-immuns, qui jouent un rôle dans la prédisposition et dans la pathogenèse des MCV. L’influence des facteurs de risque traditionnels pour les MCV (par exemple, le tabagisme, l’hypertension, le diabète, l’obésité, la sédentarité, la dépression, l’anxiété et les antécédents familiaux) est plus importante chez les femmes que chez les hommes. Enfin, il existe des différences entre les sexes dans la réponse aux traitements du risque de MCV et des processus pathologiques comorbides. Dans ce chapitre de l’Atlas, nous passons en revue les facteurs de risque de MCV propres au sexe et au genre qui peuvent survenir tout au long de la vie d’une femme, dans le but de réduire les lacunes dans les connaissances et d’orienter l’élaboration de stratégies optimales de sensibilisation et de traitement.

The conventional approach to cardiac magnetic resonance (CMR) involving breath holds, electrocardiography-gating, and acquisition of a short-axis (SAX) image stack, introduces technical and logistical challenges for assessing exercise left ventricular (LV) function. Real-time, free-breathing CMR acquisition of long-axis (LAX) images overcomes these issues and also enables assessment of global longitudinal strain (GLS). We evaluated the reliability of a free-breathing LAX approach compared to the standard SAX approach and the reproducibility of free-breathing LAX. LV SAX (contiguous stack) and LAX (two-chamber and four-chamber) 3T CMR cine images were acquired four times within one scan in 32 women with cardiovascular risk factors (56±10 years, 28±4 kg/m2) as follows: 1) resting, gated-segmented, end-expiration breath-hold; 2) resting, real-time, free-breathing; 3) test-retest set of resting, real-time, free-breathing; 4) peak exercise (incremental-to-maximum, in-magnet, stepper test), real-time, free-breathing. A second scan was performed within one week in a subset (n = 5) to determine reproducibility of peak exercise measures. Reliability and agreement of the free-breathing LAX approach with the conventional SAX approach were assessed by intraclass correlation coefficient (ICC) and Bland-Altman plots, respectively. Normal control GLS reserve was also acquired in a separate set of 12 young, healthy control women (25±4 years, 22±2 kg/m2) for comparison. Comparisons of LV volumes and function among all techniques at rest had good-to-excellent reliability (ICC = 0.80–0.96), and excellent reliability between peak exercise free-breathing LAX and SAX evaluations (ICC = 0.92–0.96). Higher resting heart rates with free-breathing acquisitions compared to breath-hold (mean difference, limits of agreement: 5, 1–12 beats per minute) reduced reliability for cardiac output (ICC = 0.67–0.79). Reproducibility of the free-breathing LAX approach was good-to-excellent at rest and peak exercise (ICC = 0.74–0.99). GLS exercise reserve was impaired in older women at cardiovascular risk compared to young healthy women (-4.7±2.3% vs -7.4±2.1%, p = 0.001). Real-time, free-breathing CMR with LAX evaluation provides a reliable and reproducible method to assess rest and peak exercise cardiac function, including GLS.

Aims An improved understanding of the pathophysiology of trastuzumab-mediated cardiotoxicity is required to improve outcomes of patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. We aimed to characterize the cardiac and cardiometabolic phenotype of trastuzumab-mediated toxicity and potential interactions with cardiac pharmacotherapy. Methods and results This study was an analysis of serial magnetic resonance imaging (MRI) and circulating biomarker data acquired from patients with HER2-positive early-stage breast cancer participating in a randomized-controlled clinical trial for the pharmaco-prevention of trastuzumab-associated cardiotoxicity. Circulating biomarkers (B-type natriuretic peptide, troponin I, MMP-2 and -9, GDF-15, neuregulin-1, and IGF-1) and MRI of cardiac structure and function and abdominal fat distribution were acquired prior to trastuzumab, post-cycle 4 and post-cycle 17. Ninety-four participants (51 ± 8 years) completed the study with 30 on placebo, 33 on perindopril, and 31 on bisoprolol. Post-cycle 4, global longitudinal strain deteriorated from baseline in both placebo (+2.0 ± 2.7%, P = 0.002) and perindopril (+0.9 ± 2.5%, P = 0.04), but not with bisoprolol (−0.2 ± 2.1%, P = 0.55). In all groups combined, extracellular volume fraction and GDF-15 increased post-cycle 4 (+1.3 ± 4.4%, P = 0.004; +130 ± 150%, P ≤ 0.001, respectively). However, no significant change in troponin I was detected throughout trastuzumab. In all groups combined, visceral and intermuscular fat volume increased post-cycle 4 (+7 ± 17%, P = 0.02, +8 ± 23%, P = 0.02, respectively), while muscle volume and IGF-1 decreased from post-cycle 4 to 17 (−2 ± 10%, P = 0.008, -18 ± 28%, P Conclusion Trastuzumab results in impaired cardiac function and early myocardial inflammation. Trastuzumab is also associated with deleterious changes to the cardiometabolic phenotype which may contribute to the increased cardiovascular risk in this population.

PURPOSE We evaluated the impact of anthracyclines on left ventricular function and myocardial tissue characteristics using cardiovascular magnetic resonance (CMR) imaging to determine their relationship with V˙O2peak. METHODS Women with breast cancer who had not yet received treatment (No-AT, n = 16) and had received anthracycline treatment ~1 yr earlier (Post-AT, n = 16) and controls without cancer (CON, n = 16) performed a maximal exercise test and a comprehensive 3T CMR examination, including native myocardial T1 mapping, where elevated T1 times are indicative of myocardial fibrosis. ANOVA and linear regression were used to compare CMR variables between groups and to determine associations with V˙O2peak. Subgroup analysis was performed by categorizing participants as "fit" or "unfit" based on whether their V˙O2peak value was greater or less than 100% of reference value for age, respectively. RESULTS Left ventricular end-diastolic volume, ejection fraction, and mass were similar between groups. Post-AT, T1 times were elevated (1534 ± 32 vs 1503 ± 28 ms, P < 0.01), and V˙O2peak was reduced (23.1 ± 7.5 vs 29.5 ± 7.7 mL·kg-1⋅min-1, P = 0.02) compared with CON. In No-AT, T1 times and V˙O2peak were similar to CON. In the Post-AT group, T1 time was associated with V˙O2peak (R2 = 64%), whereas in the absence of anthracyclines (i.e., No-AT and CON groups), T1 time was not associated with V˙O2peak. Regardless of group, all fit women had similar T1 times, whereas unfit women Post-AT had higher T1 than unfit CON (1546 ± 22 vs 1500 ± 33 ms, P < 0.01). CONCLUSIONS After anthracycline chemotherapy, an elevated T1 time suggesting greater extent of myocardial fibrosis, was associated with lower V˙O2peak. However, those who were fit did not have evidence of myocardial fibrosis after anthracycline treatment.

This study explored the perspectives and experiences of breast cancer patients and medical oncologists with regards to participation in a lifestyle intervention at a tertiary cancer treatment center. A thematic approach was used to understand the context within which a lifestyle intervention was recommended and experienced, to inform future lifestyle programming and promote uptake. Twelve women with breast cancer receiving adjuvant chemotherapy and eight medical oncologists completed interviews. Findings suggest receiving a prescription for a lifestyle intervention from a trusted health professional was influential to women with breast cancer. The intervention offered physical, psychological, emotional, social, and informational benefits to the women and oncologists perceived both physiological and relational benefit to prescribing the intervention. Challenges focused on program access and tailored interventions. Lifestyle prescriptions are perceived by women with breast cancer to have numerous benefits and may promote lifestyle interventions and build rapport between oncologists and women. Oncology healthcare professionals play a pivotal role in motivating women&rsquo, s participation in lifestyle interventions during breast cancer treatment. Maintenance programs that transition patients into community settings and provide on-going information and follow-up are needed.

This study compared the odds of self-reported and objectively measured cardiovascular (cv) risk factors in a sample of Canadian cancer survivors and individuals without cancer. A nationally representative sample of 45- to 85-year-old cancer survivors (n = 6288) in the Canadian Longitudinal Study on Aging were compared with individuals without cancer (n = 44,051). The most prevalent risk factors in cancer survivors were all self-reported or easily measured in clinic: overweight or obesity (68.0%), former smoking (62.9%), fewer than 5 daily servings of fruits and vegetables (59.8%), hypertension (43.7%), and high waist circumference (47.0%). After adjustment for sex and education, the odds ratios of several cv risk factors varied by age in cancer survivors and the non-cancer controls. At ages 50 and 60, cancer survivors have increased odds of overweight or obesity, former smoking, hypertension, high waist circumference and truncal fat, diabetes, lung disease, and heart rate greater than 80 bpm compared with non-cancer controls. At age 70, odds did not differ for many risk factors, at age 80, no differences were evident. Without modification by age, low physical activity was more prevalent in cancer survivors (odds ratio: 1.27, 95% confidence interval: 1.17 to 1.39). There were no differences in the odds of cv risk factors measured by specialized equipment, including electrocardiography, carotid ultrasonography, spirometry, and dual-energy X-ray absorptiometry. The odds of several easy-to-assess cv disease risk factors are higher among middle-aged, but not older, cancer survivors relative to the general Canadian population. Initial assessment of cv risk for middle-aged adults in the survivorship setting could be quickly and inexpensively performed using self-reported and easily measured metrics.

Objectives To examine and summarize current international guidelines regarding cardiovascular risk reduction before and during cancer therapy, and to discuss the emerging role of cardio-oncology as a subspecialty in cancer care and the role of cardio-oncology rehabilitation. Data Sources Published articles and guidelines. Conclusion With improvements in cancer detection and the use of novel adjuvant therapies, an increasing number of individuals now survive a cancer diagnosis. However, for some the cost is high — many survivors are now at higher risk of death from cardiovascular disease than from recurrent cancer. Cardiovascular morbidity and mortality are common and associated with common cancer therapies serially administered in adult oncology care. Implications for Nursing Practice Timely risk-reduction interventions hold promise in reducing cardiovascular morbidity and mortality. Oncology nurses are the key providers to identify baseline risks, perform necessary referrals, provide individualized teaching, and support the patient within the family and community.

Preclinical data demonstrate the potential for exercise training to protect against anthracycline-related cardiotoxicity, but this remains to be shown in humans. To assess whether exercise training during anthracycline-based chemotherapy for treatment of breast cancer affects resting cardiac function and hemodynamics. 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. 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

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.

Infusion therapy involves the administration of medication through a needle or catheter. In the context of cancer, infusion is a common delivery method for chemotherapy or immunotherapy. Exercise has been shown to improve several of the common side effects of chemotherapy, as well as help individuals to maintain their physical function and quality of life during treatment. The 2019 American College of Sports Medicine (ACSM) Roundtable Guidelines on Exercise for Cancer Survivors reported that specific doses of aerobic, combined aerobic plus resistance training, and/or resistance training could improve anxiety, depressive symptoms, fatigue, physical functioning, and health-related quality of life. Less is known about the role of exercise concurrent with immunotherapy. A key consideration for developing and delivering an exercise prescription during chemotherapy is that the goal of an exercise prescription may focus more on preserving rather than improving physical fitness and quality of life, which both commonly decrease during chemotherapy without a concurrent exercise intervention. Novel approaches to exercise prescription to address the side effects of chemotherapy are being investigated in optimizing exercise adherence and efficacy. While exercise is generally safe for individuals receiving chemotherapy, safety considerations remain, and exercise professionals must be aware of these key considerations and continue to monitor and assess the exercise prescription during chemotherapy.

For polar marine mammals, the energetic cost of thermoregulation depends on ambient conditions in the highly variable surrounding environment. Heat conservation strategies used by pinnipeds to reduce total heat loss include small surface area to volume ratios, the ability to limit perfusion and thick subcutaneous blubber layers. There are limits to how cool the skin surface may remain without compromising function, especially during the annual pelage molt, when hair and skin are replaced. To determine if actively molting seals incur higher thermoregulatory costs, surface temperature (ST) and heat flux (HF) were measured in 93 adult female Weddell seals (Leptonychotes weddellii) both prior to and during the active molting period using direct sensors and infrared imaging. Linear mixed-effect models revealed that ST increased significantly with increased ambient temperature and decreased wind speed (contributing 44.6 and 41.7% of the attributed variance, respectively). Seal STs were not impacted by molt status, but were maintained at 11.2 ± 0.3°C warmer than the ambient temperature. Infrared imaging results averaged 15.1 ± 1.4°C warmer than direct ST measurements. In contrast, HF was significantly higher in seals in early molting stages compared to the pre-molt season ( P

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.

Papillomaviridae is a diverse family of circular, double-stranded DNA (dsDNA) viruses that infect a broad range of mammalian, avian and fish hosts. While papillomaviruses have been characterized most extensively in humans, the study of non-human papillomaviruses has contributed greatly to our understanding of their pathogenicity and evolution. Using high-throughput sequencing approaches, we identified 7 novel papillomaviruses from vaginal swabs collected from 81 adult female Weddell seals (Leptonychotes weddellii) in the Ross Sea of Antarctica between 2014-2017. These seven papillomavirus genomes were amplified from seven individual seals, and six of the seven genomes represented novel species with distinct evolutionary lineages. This highlights the diversity of papillomaviruses among the relatively small number of Weddell seal samples tested. Viruses associated with large vertebrates are poorly studied in Antarctica, and this study adds information about papillomaviruses associated with Weddell seals and contributes to our understanding of the evolutionary history of papillomaviruses.

Exercise during chemotherapy is suggested to provide clinical benefits, including improved chemotherapy completion. Despite this, few randomized controlled exercise trials have reported on such clinical endpoints. From the OptiTrain trial we previously showed positive effects on physiological and health-related outcomes after 16 weeks of supervised exercise in patients with breast cancer undergoing chemotherapy. Here, we examined the effects of exercise on rates of chemotherapy completion and hospitalization, as well as on blood cell concentrations during chemotherapy.Two hundred forty women scheduled for chemotherapy were randomized to 16 weeks of resistance and high-intensity interval training (RT-HIIT), moderate-intensity aerobic and high-intensity interval training (AT-HIIT), or usual care (UC). Outcomes included chemotherapy completion, hospitalization, hemoglobin, lymphocyte, thrombocyte, and neutrophil concentrations during chemotherapy.No significant between-groups differences were found in the proportion of participants who required dose reductions (RT-HIIT vs. UC: odds ratio [OR], 1.08; AT-HIIT vs. UC: OR, 1.39), or average relative dose intensity of chemotherapy between groups (RT-HIIT vs. UC: effect size [ES], 0.08; AT-HIIT vs. UC: ES, -0.07). A significantly lower proportion of participants in the RT-HIIT group (3%) were hospitalized during chemotherapy compared with UC (15%; OR, 0.20). A significantly lower incidence of thrombocytopenia was found for both RT-HIIT (11%) and AT-HIIT (10%) versus UC (30%; OR, 0.27; OR, 0.27).No beneficial effects of either RT-HIIT or AT-HIIT on chemotherapy completion rates were found. However, combined resistance training and high-intensity interval training were effective to reduce hospitalization rates, and both exercise groups had a positive effect on thrombocytopenia. These are important findings with potential positive implications for the health of women with breast cancer and costs associated with treatment-related complications.Completing the prescribed chemotherapy regimen is strongly associated with a good prognosis for patients with primary breast cancer. Despite this, treatment-induced side effects make it necessary to reduce or alter the treatment regimen and can also lead to hospitalization. Exercise during chemotherapy is suggested to provide clinical benefits, including improved chemotherapy completion. This study showed that combined resistance and high-intensity interval training during chemotherapy resulted in lower hospitalization rates and a lower incidence of thrombocytopenia in women with breast cancer undergoing chemotherapy. However, no beneficial effects of either exercise program on chemotherapy completion rates were found, which is in contrast to previous findings in this population. The findings reported in the current article have positive implications for the health of women with breast cancer and costs associated with treatment-related complications.

Background: Cardiac dysfunction is a major concern for patients with breast cancer (BC) receiving adjuvant therapy. Retrospective, cross-sectional echocardiographic data suggests that patients with cancer have reduced myocardial strain prior to cancer therapy exposure. Cardiac magnetic resonance (CMR) is the gold standard imaging modality for cardiac structure and function and can also evaluate myocardial micro-architecture with T1 mapping. We hypothesized that treatment naïve patients with early-stage BC (ESBC) have abnormal myocardial tissue characteristics on CMR. Methods: Women with newly diagnosed ESBC were prospectively recruited for CMR prior to cancer drug treatment. Those with hypertension, diabetes mellitus or prior cancer treatments were excluded. Age and sex matched healthy controls were identified from a prior prospective study. All participants underwent a non-contrast CMR scan on a 1.5T magnet. Image acquisition included cines for cardiac structure and function as well as T1 mapping using saturation recovery single-shot acquisitions. Global longitudinal strain (GLS) was derived from cine images. Demographics and imaging metrics for healthy controls and patients were compared using two-sample t-test. Results: 106 patients with ESBC, mean age 51±9, were included along with 55 matched healthy controls. Body mass index and systolic blood pressure were similar between groups, however resting heart rate was elevated in patients compared to controls, 77±11 vs 67±11 /min respectively, p Conclusions: The cardiac phenotype of patients with ESBC is characterized by relative left ventricular hypertrophy with normal myocardial tissue. Further understanding of the mechanisms involved may provide insight into the cardiovascular risk associated with BC diagnosis. Table 1.Demographics Healthy Controls (n=55)Breast Cancer (n=106)P valueAge, years (SD)52(14)51(9)0.49Body mass index, kg/m2 (SD)26(5)27(6)0.38Hypertension, number00NADiabetes Mellitus, number00NAReceptor status, number (%) NAER/PRNA92(87%) HER2NA74(70%) Triple negativeNA2(2%) Stage, number (%) NA1NA43(42%) 2NA41(38%) 3NA23(20%) Systolic blood pressure, mmHg (SD)127(15)124(13)0.19Heart rate, /min (SD)67(11)77(11) Table 2.Cardiac Magnetic Resonance Healthy Controls (n=55)Breast Cancer (n=106)P valueLVEF, % (SD)62(4)62(5)0.91Indexed LVEDV, ml/m2 (SD)69(9)72(14)0.18Indexed LV mass, g/m2 (SD)47(6)52(6) Citation Format: Kirkham A, Xu L, Wang H, Chow K, Pagano JJ, White J, Haykowsky MJ, Dyck JR, Ezekowitz JA, Oudit GY, Mackey JR, Thompson RB, Pituskin E, Paterson I. Breast cancer diagnosis is associated with relative left ventricular hypertrophy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-03-07.