Cancer is considered a major global public health problem. It was estimated that in 2022 approximately 19.9 million new cancer cases were diagnosed worldwide, and this number is expected to increase over the next two decades to 28.0 million (1). Specifically, breast cancer (BC) represents the highest incidence worldwide, with approximately 2.3 million new cases diagnosed in 2022 (1). A higher incidence of BC is observed in developed countries, which may be due to high rates of obesity, alcohol and tobacco consumption, early onset of puberty, the use of contraceptives and hormonal therapies, low levels of physical activity, and giving birth at later ages (2,3). In addition to the factors mentioned above, hereditary factors and age also represent risk factors for cancer development (2,3). Finally, the presence of family members with breast and/or ovarian cancer carrying mutations in the BRCA1 or BRCA2 genes, among others, which increase the likelihood of tumor proliferation, as well as age over 40 years, also increase the probability of developing BC (2,3). Specifically, there is a molecular subtype that does not respond to hormonal receptors or HER2 and may be more aggressive and have fewer specific treatment options, known as triple-negative breast cancer (TNBC). Metabolic flexibility (MF) is described as the ability of the body to adapt to energy demands in different contexts. During chemotherapy and after surgery, significant changes may occur, such as increased body fat, loss of muscle mass, cancer-related fatigue, metabolic alterations, and decreased quality of life. These changes may persist even years after treatment and may affect both well-being and recovery. It could therefore be suggested that metabolic flexibility in muscle fibers in patients with TNBC may be reduced, particularly in patients undergoing systemic treatment, with potential difficulties adapting to different intensities and energy demands in daily life. A decrease in muscle metabolic flexibility would also imply a reduction in muscle strength and physical function, significantly impairing quality of life. Therefore, the main objective of this study is to analyze muscle metabolic flexibility at different stages of early disease and to evaluate whether different types of exercise training can improve these outcomes. To achieve this, assessments will be conducted at four time points during the early stages of the disease: at diagnosis, after neoadjuvant treatment, after surgery, and following an exercise intervention. The assessments will include blood analyses, body composition measurements, cycling exercise tests to evaluate oxygen consumption and the utilization of fat and glucose, measurements of muscle strength, and questionnaires assessing fatigue and quality of life. After surgery, participants will be randomly assigned to one of four groups for 12 weeks: a control group receiving general physical activity recommendations; a moderate-intensity cardiovascular exercise group focused on maximal fat oxidation; a high-intensity interval cardiovascular exercise group; and a progressive resistance training group. The final objective is to determine which type of exercise most effectively improves metabolic flexibility, muscle strength, body composition, and overall well-being. Participation in the study is voluntary and does not affect standard medical care. All assessments and training sessions will be supervised by qualified exercise professionals to ensure participant safety.
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Respiratory Exchange Ratio (RER)
Timeframe: 1 week after diagnosis (baseline); 1 week after completion of neoadjuvant treatment; 4 weeks after breast surgery or upon surgeon approval; and 1 week after completion of the exercise intervention or control period.
Fat Oxidation (FATox)
Timeframe: 1 week after diagnosis (baseline); 1 week after completion of neoadjuvant treatment; 4 weeks after breast surgery or upon surgeon approval; and 1 week after completion of the exercise intervention or control period.
Carbohydrate Oxidation (CHOox)
Timeframe: 1 week after diagnosis (baseline); 1 week after completion of neoadjuvant treatment; 4 weeks after breast surgery or upon surgeon approval; and 1 week after completion of the exercise intervention or control period.
Energy Expenditure
Timeframe: 1 week after diagnosis (baseline); 1 week after completion of neoadjuvant treatment; 4 weeks after breast surgery or upon surgeon approval; and 1 week after completion of the exercise intervention or control period.
Lactate Concentration
Timeframe: 1 week after diagnosis (baseline); 1 week after completion of neoadjuvant treatment; 4 weeks after breast surgery or upon surgeon approval; and 1 week after completion of the exercise intervention or control period.