Protective role of exercise on breast cancer-related osteoporosis in women undergoing aromatase inhibitors: A narrative review.

Hormone therapy following surgery reduces the risk of breast cancer (BC) recurrence and progression of hormone-sensitive BC, especially in postmenopausal women. Despite the antitumor efficacy of hormone therapy, particularly of aromatase inhibitors, they cause long-term side effects, mainly bone density reduction. Exercise can slow the rate of bone loss, which reduces the risk of fractures from osteoporosis, and could be an integrative treatment able to mitigate the BC treatment side effects positively impacting bone health. This narrative review aims to discuss studies on the effect of exercise on bone health in BC women undergoing aromatase inhibitors, highlighting the possible role of exercise as complementary to conventional therapies. Additionally, according to the literature revision, exercise practical applications to improve bone health in these patients are summarized.

The impact of physical activity on promoter-specific methylation of genes involved in the redox-status and disease progression: A longitudinal study on post-surgery female breast cancer patients undergoing medical treatment.

Most anticancer treatments act on oxidative-stress pathways by producing reactive oxygen species (ROS) to kill cancer cells, commonly resulting in consequential drug-induced systemic cytotoxicity. Physical activity (PA) has arisen as an integrative cancer therapy, having positive health effects, including in redox-homeostasis. Here, we investigated the impact of an online supervised PA program on promoter-specific DNA methylation, and corresponding gene expression/activity, in 3 antioxidants- (SOD1, SOD2, and CAT) and 3 breast cancer (BC)-related genes (BRCA1, L3MBTL1 and RASSF1A) in a population-based sample of women diagnosed with primary BC, undergoing medical treatment. We further examined mechanisms involved in methylating and demethylating pathways, predicted biological pathways and interactions of exercise-modulated molecules, and the functional relevance of modulated antioxidant markers on parameters related to aerobic capacity/endurance, physical fatigue and quality of life (QoL). PA maintained levels of SOD activity in blood plasma, and at the cellular level significantly increased SOD2 mRNA (≈+77 %), contrary to their depletion due to medical treatment. This change was inversely correlated with DNA methylation in SOD2 promoter (≈-20 %). Similarly, we found a significant effect of PA only on L3MBTL1 promoter methylation (≈-25 %), which was inversely correlated with its mRNA (≈+43 %). Finally, PA increased TET1 mRNA levels (≈+15 %) and decreased expression of DNMT3B mRNA (≈-28 %). Our results suggest that PA-modulated DNA methylation affects several signalling pathways/biological activities involved in the cellular oxidative stress response, chromatin organization/regulation, antioxidant activity and DNA/protein binding. These changes may positively impact clinical outcomes and improve the response to cancer treatment in post-surgery BC patients.

Online Home-Based Physical Activity Counteracts Changes of Redox-Status Biomarkers and Fitness Profiles during Treatment Programs in Postsurgery Female Breast Cancer Patients.

Breast cancer (BC) is one of the most commonly diagnosed types of cancer in women. Oxidative stress may contribute to cancer etiology through several mechanisms. A large body of evidence indicates that physical activity (PA) has positive effects on different aspects of BC evolution, including mitigation of negative effects induced by medical treatment. With the aim to verify the capacity of PA to counteract negative effects of BC treatment on systemic redox homeostasis in postsurgery female BC patients, we have examined the modulation of circulating levels of oxidative stress and inflammation markers. Moreover, we evaluated the impacts on physical fitness and mental well-being by measuring functional parameters, body mass index, body composition, health-related quality of life (QoL), and fatigue. Our investigation revealed that PA was effective in maintaining plasma levels of superoxide dismutase (SOD) activity and tGSH, as well as peripheral blood mononuclear cells' (PBMCs) mRNA levels of SOD1 and heat-shock protein 27. Moreover, we found a significant decrease in plasma interleukin-6 (≈0.57 ± 0.23-fold change, p < 0.05) and increases in both interleukin-10 (≈1.15 ± 0.35-fold change, p < 0.05) and PBMCs' mRNA level of SOD2 (≈1.87 ± 0.36-fold change, p < 0.05). Finally, PA improves functional parameters (6 min walking test, ≈+6.50%, p < 0.01; Borg, ≈-58.18%, p < 0.01; sit-and-reach, ≈+250.00%, p < 0.01; scratch right, ≈-24.12%, and left, ≈-18.81%, p < 0.01) and body composition (free fat mass, ≈+2.80%, p < 0.05; fat mass, ≈-6.93%, p < 0.05) as well as the QoL (physical function, ≈+5.78%, p < 0.05) and fatigue (cognitive fatigue, ≈-60%, p < 0.05) parameters. These results suggest that a specific PA program not only is effective in improving functional and anthropometric parameters but may also activate cellular responses through a multitude of actions in postsurgery BC patients undergoing adjuvant therapy. These may include modulation of gene expression and protein activity and impacting several signaling pathways/biological activities involved in tumor-cell growth; metastasis; and inflammation, as well as moderating distress symptoms known to negatively affect QoL.

Kinesiology Students' Perception Regarding Exercise Oncology: A Cross-Sectional Study.

Delivering physical activity in cancer care requires knowledge, competence, and specific skills to adapt the exercise program to the patients' specific needs. Kinesiology students could be one of the main stakeholders involved in the promotion of physical activity. This study aims to investigate the knowledge, perception, and competence about exercise in patients with oncological disease in a sample of students attending the Sports Science University. A total of 854 students (13% response rate) from four Italian universities completed the online survey between May and June 2021. About half of the study participants identified the correct amount of aerobic (44%) and strength (54%) activities proposed by the American College of Sports Medicine for patients with cancer. Almost all the students recognized the importance of physical activity in cancer prevention (96%), in the management of cancer before surgery (96%), during anticancer treatments (84%), and after therapies completion (98%). On the contrary, they reported a lack of university courses dedicated to cancer diseases, psychological implications, and prescription of physical activity in all types of cancer prevention. Overall, few students felt qualified in delivered counseling about physical activity and individual or group-based exercise programs in patients with cancer. Logistic regression revealed that the students attending the Master's Degree in Preventive and Adapted Physical Activity were more likely to have knowledge and competence than other students. The present study suggests that kinesiology universities should increase the classes and internships about exercise oncology to train experts with specific skills who are able to adequately support patients in their lifestyle modification.

The Beneficial Role of Physical Exercise on Anthracyclines Induced Cardiotoxicity in Breast Cancer Patients.

The increase in breast cancer (BC) survival has determined a growing survivor population that seems to develop several comorbidities and, specifically, treatment-induced cardiovascular disease (CVD), especially those patients treated with anthracyclines. Indeed, it is known that these compounds act through the induction of supraphysiological production of reactive oxygen species (ROS), which appear to be central mediators of numerous direct and indirect cardiac adverse consequences. Evidence suggests that physical exercise (PE) practised before, during or after BC treatments could represent a viable non-pharmacological strategy as it increases heart tolerance against many cardiotoxic agents, and therefore improves several functional, subclinical, and clinical parameters. At molecular level, the cardioprotective effects are mainly associated with an exercise-induced increase of stress response proteins (HSP60 and HSP70) and antioxidant (SOD activity, GSH), as well as a decrease in lipid peroxidation, and pro-apoptotic proteins such as Bax, Bax-to-Bcl-2 ratio. Moreover, this protection can potentially be explained by a preservation of myosin heavy chain (MHC) isoform distribution. Despite this knowledge, it is not clear which type of exercise should be suggested in BC patient undergoing anthracycline treatment. This highlights the lack of special guidelines on how affected patients should be managed more efficiently. This review offers a general framework for the role of anthracyclines in the physio-pathological mechanisms of cardiotoxicity and the potential protective role of PE. Finally, potential exercise-based strategies are discussed on the basis of scientific findings.

The Impact of Functional Bars and Adapted Physical Activity on Quality of Life in Chronic Kidney Disease: A Pilot Study.

Chronic kidney disease (CKD) represents a public health problem because it is characterized by several comorbidities, including uremic sarcopenia (US), and a poor quality of life. Currently, there are no standardized treatments available to counteract the onset of US but only some possible therapeutic approaches to slow its progression. The aim of this pilot study is to collect descriptive data in order to design a clinical trial based on the power analysis and simple size. The purpose of this pilot study was to evaluate the possible beneficial action induced by the functional anti-inflammatory and antioxidant bars in combination with the adapted physical activity (APA), on the onset and progression of US and other related-CKD comorbidities. We enrolled 21 CKD patients under conservative therapy, divided into four groups: (A) the physical exercise program (PEP), three times a week, in combination with the daily consumption of the two functional bars group; (B) the PEP group; (C) the daily consumption of the two functional bars group; (D) the control group. The duration of the study protocol was 12 weeks. We observed an improvement trend of body composition, blood pressure levels, lipid metabolism, and functional test in A and B groups. These preliminary data would seem to confirm the effectiveness of APA and to demonstrate the additive role of the natural bioactive compound's assumption in countering US and other CKD comorbidities.

"OPERATION PHALCO"-Adapted Physical Activity for Breast Cancer Survivors: Is It Time for a Multidisciplinary Approach?

The international literature emphasizes the importance of physical activity (PA) in the first steps after cancer surgery. The regular practice of physical exercise causes positive adaptations on several functional capacities, with positive consequences on patients' quality of life. This project aims to evaluate the effect of a post-operative training protocol, structured by taking into account both cancer-related issues and the presence of comorbidities, on functional capacities and quality of life of breast cancer survivors. Therefore, it was necessary to create a synergy between oncologists (referring physicians), sport medicine physicians (risk stratification and exercise prescription) and kinesiologists (trainers). Thirty-five post-surgery BC patients decided on a voluntary basis to attend an online Adapted PA (APA) protocol for 4 months, twice a week (APA Group) or Usual Care Group (UC Group). Functional capacity of the APA Group significantly increased, by 13.1% (p = 0.000), whereas perceived exertion decreased by 19.7% (p = 0.020). In the same group, the general health evaluated through the questionnaire EORTC-QLQ-C30 increased (p = 0.050). No differences were found in the UC Group. Operation Phalco, creating a network between oncologists, sports medicine physicians and kinesiologists, confirms the importance of structuring a post-operative path where APA should be included as early as possible in the cancer patient care.

Estrogen-Receptor-Positive Breast Cancer in Postmenopausal Women: The Role of Body Composition and Physical Exercise.

Breast cancer (BC) is the most commonly diagnosed cancer among women worldwide and the most common cause of cancer-related death. To date, it is still a challenge to estimate the magnitude of the clinical impact of physical activity (PA) on those parameters producing significative changes in future BC risk and disease progression. However, studies conducted in recent years highlight the role of PA not only as a protective factor for the development of ER+ breast cancer but, more generally, as a useful tool in the management of BC treatment as an adjuvant to traditional therapies. In this review, we focused our attention on data obtained from human studies analyzing, at each level of disease prevention (i.e., primary, secondary, tertiary and quaternary), the positive impact of PA/exercise in ER+ BC, a subtype representing approximately 70% of all BC diagnoses. Moreover, given the importance of estrogen receptors and body composition (i.e., adipose tissue) in this subtype of BC, an overview of their role will also be made throughout this review.

Impact of Physical Activity and Natural Bioactive Compounds on Endothelial Dysfunction in Chronic Kidney Disease.

Chronic kidney disease (CKD) represents a world-wide public health problem. Inflammation, endothelial dysfunction (ED) and vascular calcifications are clinical features of CKD patients that increase cardiovascular (CV) mortality. CKD-related CV disease pathogenic mechanisms are not only associated with traditional factors such as arterial hypertension and dyslipidemia, but also with ED, oxidative stress and low-grade inflammation. The typical comorbidities of CKD contribute to reduce the performance and the levels of the physical activity in nephropathic patients compared to healthy subjects. Currently, the effective role of physical activity on ED is still debated, but the available few literature data suggest its positive contribution. Another possible adjuvant treatment of ED in CKD patients is represented by natural bioactive compounds (NBCs). Among these, minor polar compounds of extra virgin olive oil (hydroxytyrosol, tyrosol and oleocanthal), polyphenols, and vitamin D seem to exert a beneficial role on ED in CKD patients. The objective of the review is to evaluate the effectiveness of physical exercise protocols and/or NBCs on ED in CKD patients.

Evaluation of a Post-Operative Rehabilitation Program in Patients Undergoing Laparoscopic Colorectal Cancer Surgery: A Pilot Study.

This pilot study explores the effects of a post-operative physical exercise program on the quality of life (QoL) and functional and nutritional parameters of patients that underwent laparoscopic colorectal cancer surgery, compared to usual care alone. The intervention group (IG) attended a 2-month-long supervised and combined exercise-training program during the post-operative period. Both IG and control group (CG) participated in the QoL, functional, and nutritional assessments before exercise training (T0), 2 months after the beginning of the exercise (end of treatment) (T1), and 2 (T2) and 4 (T3) months from the end of treatment. Eleven patients with colorectal cancer that underwent laparoscopic surgery were enrolled (six intervention; five control). The IG showed significant improvements compared to the CG in "Physical functioning" (PF2) (p = 0.030), "Cognitive functioning" (CF) (p = 0.018), and "Fatigue" (FA) (p = 0.017) of the European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) at T1; in SMWT (p = 0.022) at T1; in PF2 (p = 0.018) and FA (p = 0.045) of EORTC QLQ-C30 at T2, in phase angle (PhA) of bioelectrical impedance analysis (p = 0.022) at T3. This pilot study shows that a post-operative, combined, and supervised physical exercise program may have positive effects in improving the QoL, functional capacity, and nutritional status in patients that undergo laparoscopic colorectal cancer surgery.

Dancing With Health: Quality of Life and Physical Improvements From an EU Collaborative Dance Programme With Women Following Breast Cancer Treatment.

Background: Women's health has received renewed attention in the last few years including health rehabilitation options for women affected by breast cancer. Dancing has often been regarded as one attractive option for supporting women's well-being and health, but research with women recovering from breast cancer is still in its infancy. Dancing with Health is multi-site pilot study that aimed to evaluate a dance programme for women in recovery from breast cancer across five European countries. Methods: A standardized 32 h dance protocol introduced a range of Latin American dances presented within a sports and exercise framework with influences from dance movement therapy. Fifty-four women (M age 53.51; SD 7.99) participated in the study who had a breast cancer diagnosis <3 years, chemotherapy >6 weeks, no indication of metastasis, or scheduled surgery/chemotherapy/radiation treatment for the duration of the intervention. Primary outcome data was collected for anthropometric and fitness measures next to cancer-related quality of life. T-tests and Wilcoxon signed ranked tests were used to establish differences pre and post intervention. Cohen's d was also calculated to determine the effect size of the intervention. Results: Statistically significant changes were found for: (i) weight, right and left forearm circumference and hip; (ii) 6 min walking, right and left handgrip, sit-to-stand and sit-and-reach; (iii) the EORTC-QLQ C30 summary score as well as the subscales of emotional and social functioning and symptoms. In all cases the direction of change was positive, while Cohen's d calculated showed that the effect of the intervention for these parameters ranged from intermediate to large. Conclusion: Changes on the above anthropometric, fitness and quality of life measures suggest that the intervention was of value to the participating women recovering from breast cancer. Results also advocate collaborative efforts across countries to further research.

AlphaB-crystallin and breast cancer: role and possible therapeutic strategies.

AlphaB-crystallin (HSPB5) is one of the most prominent and well-studied members of the small heat shock protein (sHsp) family. To date, it is known that this protein modulates significant cellular processes and therefore, it is not surprising that its deregulation is involved in various human pathologies, including cancer diseases. Despite the pathogenic significance of HSPB5 in cancer and its regulatory mechanism related to aggressiveness is poorly understood, several reports describe the association of breast carcinoma progression with HSPB5, whose expression is also considered an independent predictor of breast cancer metastasis to the brain. Indeed, numerous authors indicate HSPB5 as a new valuable biomarker for clinicopathological parameters and poor prognosis in breast cancer. Considering the cytoprotective, anti-apoptotic, pro-angiogenic, and pro-metastatic properties of the sHsps, it is not surprising that they are considered as promising targets for anticancer treatment, even though, at present, a deeper understanding of their mode of action is needed to allow the development of precise therapeutic interventions. Data on the direct inhibition of different sHsps demonstrate promising results in cancer pathologies; however, specific strategies against HSPB5 have not been considered. This review highlights the most relevant findings on HSPB5 and its role in breast cancer, as well as the possible strategies in using HSPB5 inhibition for therapeutic purposes.

Exercise-mediated downregulation of MALAT1 expression and implications in primary and secondary cancer prevention.

Long non-coding RNAs (lncRNAs) play critical roles in various biological functions and disease processes including cancer. The metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was initially identified as a lncRNA with elevated expression in primary human non-small cell lung tumors with high propensity to metastasize, and subsequently shown to be highly expressed in numerous other human cancers including breast, ovarian, prostate, cervical, endometrial, gastric, pancreatic, sarcoma, colorectal, bladder, brain, multiple myeloma, and lymphoma. MALAT1 is deeply involved in several physiological processes, including alternative splicing, epigenetic modification of gene expression, cellular senescence, healthy aging, and redox homeostasis. The aim of this work was to investigate the modulation exerted by a single bout of endurance exercise on the level of MALAT1 expression in peripheral blood mononuclear cells (PBMCs) from healthy male donors displaying different training status and redox homeostasis features. Our findings show that MALAT1 is downregulated after acute endurance exercise in subjects whose fitness level guarantee a high expression of SOD1 and SOD2 antioxidant genes and low levels of endogenous oxidative damage. In vitro protocols in Jurkat lymphoblastoid cells exposed to pro-oxidant environment confirmed the link between MALAT1 expression and antioxidant gene modulation, documenting p53 phosphorylation and its recruitment to MALAT1 promoter. Remarkably, analyses of Microarray-Based Gene Expression Profiling revealed high MALAT1 expression in leukemia patients in comparison to healthy control and a significant negative correlation between MALAT1 and SOD1 expression. Collectively our results highlight the beneficial effect of a physically active lifestyle in counteracting aberrant cancer-related gene expression programs by improving the redox buffering capacity.

Physical activity in the prevention of human diseases: role of epigenetic modifications.

Epigenetic modification refers to heritable changes in gene function that cannot be explained by alterations in the DNA sequence. The current literature clearly demonstrates that the epigenetic response is highly dynamic and influenced by different biological and environmental factors such as aging, nutrient availability and physical exercise. As such, it is well accepted that physical activity and exercise can modulate gene expression through epigenetic alternations although the type and duration of exercise eliciting specific epigenetic effects that can result in health benefits and prevent chronic diseases remains to be determined. This review highlights the most significant findings from epigenetic studies involving physical activity/exercise interventions known to benefit chronic diseases such as metabolic syndrome, diabetes, cancer, cardiovascular and neurodegenerative diseases.