Effects of combined training in the c-miRNAs expression in women with Breast Cancer

• Grant number: 20/06262-0
• Support type: Scholarships in Brazil - Doctorate
• Effective date (Start): March 01, 2021
• Effective date (End): October 31, 2023
• Field of knowledge: Health Sciences - Physical Education
• Principal researcher: Carlos Ugrinowitsch
• Grantee: Guilherme Defante Telles
• Home Institution: Escola de Educação Física e Esporte (EEFE). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Combined Training (CT) has been identified as a non-pharmacological strategy to improve health and quality of life of women with Breast Cancer. It is suggested that this improvement occurs both through the increase in muscle mass and cardiorespiratory fitness, as well as through intrinsic effects directly on the tumor, possibly with the expression of circulating microRNAs (c-miRNAs) inserted in extracellular vesicles. Hypotheses: The CT performed before the treatment of Breast Cancer will improve the functionality and quality of life (health) of women, will increase the efficiency of Cancer treatment, reducing tumor proliferation and these improvements / effects will be related to the decrease in expression of circulating oncomiRs, as well as increased expression of c-miRNAs related to tumor suppression, in extracellular vesicles. Final Aim: To investigate the effects of combined training conducted before Breast Cancer treatment on women's health and the molecular mechanisms related to these effects. Specific: 1) Acute effect (transient, after a CT session): knowing that the acute response of systemic factors induced by exercise can affect tumor development, we will test whether the expression of c-miRNAs after a CT session changes in magnitude and specificity of the PRE moment for the POST training ; 2) Chronic effect (after CT intervention): knowing that CT can change the basal expression of c-miRNAs, we want to know if changes in functionality and quality of life, as well as possible changes in tumor development, induced by CT, the possible changes in c-miRNAs from pre to post training are associated; 3) Retention effect: we want to know if the chronic effects induced by CT are maintained after the Cancer treatment (post retention moment) and if this retention is associated with the treatment effectiveness in the tumor. Methods: 100 women diagnosed with Breast Cancer will be allocated to one of the following groups: CT (CT, n = 50), or control group (CG, n = 50). CT will be performed three times a week, consisting of resistance training (8 exercises, 1-3 sets of 8-12 RM at 70% 1-RM) followed by aerobic training (3-4 sets of 3 min at 90% of the maximum oxygen consumption (VO2máx) with 3 min of active recovery (30% of VO2máx) in the cycle ergometer. To analyze the dependent variables, the thigh magnetic resonance test, of a maximum repetition (1-RM), densitometry of dual absorption of X-rays (DXA), VO2max, sit and stand and timed up and go, FACT-B and FACIT-F questionnaires, Ki67 analysis (tumor proliferation) and Residual Cancer Burden. The levels of c-miRNAs will be measured from the nanoString technique Cancer; 2) determine the effect of a CT program carried out in the period between the diagnosis of Breast Cancer and before the beginning of treatment on baseline levels of c-miRNAs inserted in extracellular vesicles and on: A) muscle mass; B) muscle strength; C) cardiorespiratory fitness; D) physical functionality; E) quality of life. Methods: 100 women diagnosed with Breast Cancer will be allocated to one of the following groups: CT (CT, n = 50), or control group (CG, n = 50). The CT will be performed three times a week, consisting of strength training (8 exercises, 1-3 sets of 8-12 RM at 70% 1-RM) followed by aerobic training (3-4 sets of 3 min at 90% of the maximum oxygen consumption (VO2máx) for 3 min of active recovery (30% of VO2máx) in the cycle ergometer. To analyze the dependent variables, the thigh magnetic resonance test, of a maximum repetition (1-RM), densitometry of double absorption of X-rays (DXA), VO2máx, sit and stand and Timed Up and Go and the FACT-B and FACT-F questionnaire The levels of c-miRNAs will be measured using the nanoString technique. (AU)