A review of research on the intersection between breast cancer and cardiovascular research in the Women’s Health Initiative (WHI)

Both obesity and metabolic syndrome are linked to increased incidence of type 2 diabetes, cardiovascular disease (CVD), and cancers of the breast (post-menopausal), and other obesity-related cancers. Over the past 50 years, the worldwide prevalence of obesity and metabolic syndrome has increased, with a concomitant higher incidence of associated co-morbidities and mortality. The precise mechanism linking metabolic syndrome to increased cancer incidence is incompletely understood, however, individual components of metabolic syndrome have been linked to increased breast cancer incidence and worse survival. There is a bidirectional relationship between the risk of CVD and cancer due to a high burden of shared risk factors and higher rates of CVD among cancer survivors, which may be impacted by the pro-inflammatory microenvironment associated with metabolic syndrome and cancer-directed therapies. The Women’s Health Initiative (WHI) is an excellent resource to study a dual relationship between cancer and CVD (cardio-oncology) with extensive information on risk factors and long-term outcomes. The purpose of this review is to provide an overview of research on cardio-oncology conducted utilizing WHI data with focus on studies evaluating both breast cancer and CVD including shared risk factors and outcomes after cancer. The review also includes results on other obesity related cancers which were included in the analyses of breast cancer, articles looking at cancer after heart disease (reverse cardio-oncology) and the role of Clonal Hematopoiesis of Indeterminate Potential (CHIP) as a shared risk factor between CVD and cancer. A summary of pertinent WHI literature helps to delineate the direction of future research evaluating the relationship between CVD and other cancer sites, and provides information on the opportunity for other novel analyses within the WHI

Fasting and Exercise in Oncology: Potential Synergism of Combined Interventions

Nutrition and exercise interventions are strongly recommended for most cancer patients; however, much debate exists about the best prescription. Combining fasting with exercise is relatively untouched within the oncology setting. Separately, fasting has demonstrated reductions in chemotherapy-related side effects and improved treatment tolerability and effectiveness. Emerging evidence suggests fasting may have a protective effect on healthy cells allowing chemotherapy to exclusively target cancer cells. Exercise is commonly recommended and attenuates treatment- and cancer-related adverse changes to body composition, quality of life, and physical function. Given their independent benefits, in combination, fasting and exercise may induce synergistic effects and further improve cancer-related outcomes. In this narrative review, we provide a critical appraisal of the current evidence of fasting and exercise as independent interventions in the cancer population and discuss the potential benefits and mechanisms of combined fasting and exercise on cardiometabolic, body composition, patient-reported outcomes, and cancer-related outcomes. Our findings suggest that within the non-cancer population combined fasting and exercise is a viable strategy to improve health-related outcomes, however, its safety and efficacy in the oncology setting remain unknown. Therefore, we also provide a discussion on potential safety issues and considerations for future research in the growing cancer population

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

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

The Effect of Exercise and Nutritional Interventions on Body Composition in Patients with Advanced or Metastatic Cancer: A Systematic Review

Advanced and metastatic cancers significantly alter body composition, leading to decreased lean mass and variable effects on fat mass. These effects on body composition are associated with significant physical dysfunction and poor prognosis in patients with cancer. Whilst exercise and nutritional interventions are likely to be of benefit in counteracting these effects, relatively little is known about using such interventions in patients with advanced or metastatic cancer. Therefore, in this systematic review we examine the effect of exercise and combined exercise and nutritional interventions on lean mass and fat mass among patients diagnosed with advanced or metastatic cancer. Following PRISMA guidelines, we identified 20 articles from PubMed, EMBASE, CINAHL, Cochrane CENTRAL, PEDro, SPORTDiscus, and REHABDATA. Overall, advanced or metastatic cancer populations comprising of mixed cancer types were most commonly examined (n = 8) with exercise or combined exercise and nutritional interventions being well-tolerated with few adverse effects. Both intervention approaches may preserve lean mass, while only combined interventions may lead to alterations in fat mass. However, further exercise and nutritional studies are needed to definitively understand their effects on body composition. As exercise and nutrition-related research continues in this understudied population, the knowledge gained will help guide supportive clinical treatments

Incorporating Exercise Training into&nbsp;Cardio-Oncology Care: Current Evidence and Opportunities: JACC: CardioOncology State-of-the-Art Review.

Cancer treatment-induced cardiotoxicities are an ongoing concern throughout the cancer care continuum from treatment initiation to survivorship. Several "standard-of-care" primary, secondary, and tertiary prevention strategies are available to prevent the development or further progression of cancer treatment-induced cardiotoxicities and their risk factors. Despite exercise's established benefits on the cardiovascular system, it has not been widely adopted as a nonpharmacologic cardioprotective strategy within cardio-oncology care. In this state-of-the-art review, the authors discuss cancer treatment-induced cardiotoxicities, review the existing evidence supporting the role of exercise in preventing and managing these sequelae in at-risk and affected individuals living after cancer diagnoses, and propose considerations for implementing exercise-based services in cardio-oncology practice

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

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