Chronic systemic response of inflammatory chemokines, muscle mass, and body fat percentage after combined training performed before treatment in women with breast cancer

• Grant number: 24/22777-1
• Support Opportunities: Scholarships in Brazil - Master
• Start date: May 01, 2025
• End date: April 30, 2027
• Field of knowledge: Health Sciences - Physical Education
• Principal Investigator: Miguel Soares Conceição
• Grantee: Dhyana Barban de Campos Lima Borin
• 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

Breast cancer, although multifactorial, is a chronic-degenerative disease often triggered by an inflammatory process. Inflammation can result from various factors, with obesity being one of the main catalysts. Excessive accumulation of adipose tissue leads to increased infiltration of metabolically activated macrophages in this tissue. These infiltrated macrophages induce and amplify the production of inflammatory mediators, such as Tumor Necrosis Factor-alpha (TNF-¿) and Interleukin-6 (IL-6), perpetuating a state of low-grade chronic inflammation. In summary, obesity not only promotes and enhances chronic inflammation, orchestrated by TNF-¿ and IL-6, but also induces excessive expression of other inflammatory mediators derived from adipose tissue, such as chemokines, creating a hormonal and metabolic environment that favors breast carcinogenesis. Typically induced by growth factors, pathogenic stimuli, immune cells, and inflammatory cytokines such as TNF-¿, Interleukin-1 (IL-1), and Interferon-gamma (IFN-¿), and expressed by lymphocytes in the bloodstream, chemokines are responsible for the migration, adhesion, interaction, and positioning of immune cells.In obesity, the exacerbated production of pro-inflammatory chemokines by adipose tissue, such as CCL2 and CXCL8, amplifies this inflammatory environment, promoting the infiltration of M2 macrophages and other inflammatory cells that sustain low-grade chronic inflammation. On the other hand, the anti-inflammatory response, generally induced by cells such as CD8+ T cells and Natural Killer (NK) cells, cytokines like IFN-¿, and chemokines like CXCR3 and its ligands, aims to reduce pro-inflammation, restore tissue homeostasis, and enhance antitumor immunity.Since the majority of breast cancer patients are overweight/obese, a strategy to reduce body fat percentage would be ideal. In this context, the combined implementation of strength and aerobic training, known as combined training (CT), is an efficient strategy to reduce body fat percentage and systemic inflammation, while increasing muscle mass and cardiorespiratory fitness. This should ideally begin before chemotherapy to mitigate its adverse effects.Thus, investigating whether CT can reduce body fat percentage and the systemic response of pro-inflammatory chemokines, while increasing muscle mass and cardiorespiratory fitness after a training period in breast cancer patients, is crucial. To achieve this, measurements of inflammatory chemokines, body composition, and cardiorespiratory fitness will be taken before and after a CT period, which will begin immediately after diagnosis and conclude before the start of treatment. This period is referred to as the window of opportunity.