EFFECTS OF COMBINED TRAINING ON TUMOR BLOOD FLOW IN BREAST CANCER PATIENTS

• Grant number: 23/14615-9
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: June 01, 2024
• End date: May 31, 2026
• Field of knowledge: Health Sciences - Physical Education
• Principal Investigator: Miguel Soares Conceição
• Grantee: Olivia Moraes Ruberti
• Host Institution: Universidade São Francisco (USF). Campus Bragança Paulista. Bragança Paulista , SP, Brazil
• Associated research grant: 21/01424-5 - Effects of combined physical training in women with Breast Cancer submitted to chemotherapy, AP.JP

Abstract

Introduction: Breast tumors exhibit an abnormal vascular system characterized by low tumor blood flow and dysfunctional angiogenesis, compromising tumor oxygenation and drug delivery. Moreover, tumor growth and neoadjuvant treatment induce impairment in muscle mass and aerobic fitness in women with breast cancer. This impairment in muscle mass, aerobic fitness, and the dysfunctional vascular system may promote tumor progression and increase metastasis risk. As resistance and aerobic training - combined training (CT) - is an efficient strategy to increase muscle mass and aerobic fitness, CT should be initiated before chemotherapy to mitigate its adverse effects. Additionally, physical training can induce changes in vascular (e.g., increased tumor blood flow) and metabolic factors, which may also contribute to the beneficial effects of physical training for women with breast cancer. Aims: To determine the effects of CT performed between diagnosis and the start of treatment in women with breast cancer on: a) tumor blood flow b) tumor perfusion c) tumor progression d) tumor metabolic profile. Furthermore, to determine the relationship between blood flow and tumor perfusion in disease progression. Methods: 100 women with breast cancer scheduled for treatment at CAISM-UNICAMP will be randomized to one of the following groups: CT before chemotherapy (CT, n=50) or control group (CG, n=50). Subsequently, these women will undergo the following assessments both before and after the CT/CG period: 1) body composition using dual-energy X-ray absorptiometry (DXA); 2) muscle strength using the one-repetition maximum test (1-RM); 3) cardiorespiratory fitness using the direct maximum oxygen consumption test (VO2max); 4) blood flow analysis by Doppler (Contrast Enhanced Ultrasound - CEUS); 5) tumor perfusion analysis using microbubble contrast. Finally, the same assessments of muscle mass, muscle strength and aerobic power, will be conducted again at the end of cancer treatment. Ultrasound analyses will be performed at four time points: 1st) before the first training session; 2nd) immediately after the first training session; 3rd) before the last training session; 4th) immediately after the last training session. CT will be performed three times per week. The CT protocol will consist of resistance training (5 exercises, 1-4 sets of 8-12 repetitions at 80-90% of 1-RM, with 2 minutes between sets) followed by aerobic training (3-5 sets of 2 minutes at 50% delta (approximately 90% of VO2max) with 3 minutes of active recovery (30% of VO2max)) on the cycle ergometer. We hypothesize that physical training before neoadjuvant chemotherapy would increase blood flow and tumor perfusion, and this increase would result in improved treatment response (tumor progression).