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.
Cancer is recognized as a major global socio-health issue. In 2022, it was estimated that approximately 19.9 million new cancer cases were diagnosed worldwide, and this number is projected to rise to 28.0 million over the next two decades (1). Breast cancer (BC) specifically exhibits the highest incidence globally, with around 2.3 million new cases reported in 2022 (1). According to the Spanish Society of Medical Oncology (SEOM), 37,682 new BC cases are expected to be diagnosed in Spain in 2025 (1). Currently, BC subtypes are classified based on their molecular characteristics (2,3). The triple-negative (TN) molecular subtype is defined by the absence of estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER2). TNBC accounts for 10-20% of invasive BC cases and is considered more biologically and clinically aggressive than other subtypes (2,3). It also presents a poorer prognosis and more limited treatment options (2,3). Metabolic flexibility (MF) refers to the body's capacity to adapt to energy demands under varying conditions (4,5). Mitochondria, as the primary cellular organelles responsible for energy production, facilitate substrate oxidation to generate ATP according to required intensity levels (5). In contrast, metabolic inflexibility in muscle fibers is characterized by impaired lactate clearance, reduced lipid oxidation capacity, and rapid switching from fat to carbohydrate (CHO) oxidation (6). Some studies suggest that cancer induces systemic mitochondrial dysfunction across multiple tissues, influenced both by disease pathophysiology and the toxicity of oncological treatments (7). Additionally, decreased PGC-1α levels have been observed in patients receiving neoadjuvant chemotherapy (NAC). PGC-1α is a key transcriptional coactivator regulating mitochondrial biogenesis, and its reduction may contribute to inefficient energy production, resulting in muscle dysfunction and loss of both mass and function in cancer patients (7,8). Moreover, women with BC who undergo chemotherapy are more likely to gain fat mass compared to age-matched women without BC (7,9,10,11). Excess adipose tissue is linked to metabolic disease and elevated pro-inflammatory cytokines, further contributing to mitochondrial and metabolic dysfunction. Increased fat mass has also been associated with higher risks of recurrence, disease progression, and mortality in BC studies (7,9,10,11). Evidence highlights the crucial role physical exercise plays in cellular metabolism. Studies demonstrate that exercise significantly influences glucose levels, insulin resistance, growth factors, fat oxidation rates, and lactate clearance (12,13). Dysregulation of these factors may activate tumor signaling pathways, posing a risk for tumor proliferation (12,13,14). Consequently, modulating metabolism through physical activity could be fundamental in influencing cancer progression (12,13,14). Exercise is key for activating the AMPK signaling pathway, an enzyme triggered under high-energy demands. Activation of AMPK promotes GLUT4 translocation, enhancing glycolysis, fatty acid (FA) oxidation, and mitochondrial biogenesis, including upregulation of PGC-1α (15,16). Continuous endurance training has been shown to sustain AMPK activation for hours post-exercise, with longer durations producing greater benefits (15,17). Similarly, high-intensity cardiovascular training appears to elevate AMPK levels hours after the activity (15,17). Alongside increased AMPK and PGC-1α activity, training has been associated with greater mitochondrial content and function in muscle fibers (4,6,16,18). This enhances fatty acid oxidation capacity in mitochondria, thereby improving metabolic flexibility (4,6,18). Altogether, these adaptations increase the ability of muscle fibers-now with more mitochondria-to utilize multiple substrates efficiently, improving MF (4,6,18,19). Recent research also indicates that increasing muscle strength and preventing fat mass gain are essential for maintaining metabolic health and optimizing treatment response, as they are associated with improvements in markers such as insulin sensitivity, glycemic control, and acute anti-inflammatory responses (20,21). Importantly, exercise-induced benefits on mitochondrial and metabolic health appear independent of weight loss from fat reduction (20,21). In summary, cancer patients-particularly those with TNBC-may experience systemic metabolic dysfunction due to disease pathophysiology, treatment toxicity, and suboptimal lifestyle habits (4,5,7,8,10,14,18,22,23,24,25,26). However, to date, no studies have described the metabolic response to exercise in this population. Thus, the primary aim of this study is to describe the metabolic flexibility of patients with early-stage TNBC across different phases of the disease. This approach may allow indirect determination of the preferred energy substrate in muscle fibers and identification of the optimal intensity for fatty acid oxidation to improve metabolic profiles in these patients. Additionally, the study will evaluate the effects of two cardiovascular training interventions and one strength training intervention on the metabolic profile of patients with early-stage TNBC. This pilot study will initially adopt a descriptive, longitudinal design, followed by an open, randomized experimental phase in early-stage TNBC patients. First, a descriptive observational analysis will be conducted, followed by an experimental study with four groups using a pre-post design, including a control group (CG). A group consisting exclusively of newly diagnosed TNBC patients (D1) meeting inclusion criteria will be established. This group will receive only general physical activity recommendations provided by the World Health Organization (WHO) during neoadjuvant treatment and prior to breast surgery. The sample will include 40 TNBC patients selected by convenience sampling from Hospital Universitario Severo Ochoa (Av. de Orellana, s/n, 28914 Leganés, Madrid), Hospital Universitario Infanta Leonor (Av. Gran Vía del Este, 80, Vallecas, 28031 Madrid), and Hospital de la Princesa (Calle de Diego de León, 62, Salamanca, 28006 Madrid), all located in the Community of Madrid. To determine the most effective exercise intervention for enhancing metabolic flexibility and function, the study will consider: the group with the highest number of patients demonstrating decreased RER and lactate during the exercise test (ET) at the end of each incremental protocol stage post-surgery compared with pre-intervention; the group with the most patients showing increased FATox and CHOox, as well as associated kcal values, at the same stage-defined ET points post-surgery; and the experimental group exhibiting statistically significant changes in these variables.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
40
Group performing cardiovascular training at maximal fat oxidation (FATmax) twice per week for 12 weeks
Group performing cardiovascular training at maximal aerobic power (MAP) twice per week for 12 weeks
Group performing progressive resistance training twice per week for 12 weeks
Universidad Europea de Madrid, Villaviciosa de Odón
Madrid, Madrid, Spain
Respiratory Exchange Ratio (RER)
The respiratory exchange ratio is the ratio of carbon dioxide production (VCO2) to oxygen consumption (VO2) measured during respiration. It is obtained through indirect calorimetry during rest or exercise and reflects substrate utilization (fat or carbohydrate oxidation).
Time frame: 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)
Fat oxidation refers to the rate at which fatty acids are used as an energy substrate by the body during rest or exercise. It is typically estimated from oxygen consumption (VO2) and carbon dioxide production (VCO2) using indirect calorimetry. FATox is commonly expressed in grams per minute (g/min).
Time frame: 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)
Carbohydrate oxidation refers to the rate at which carbohydrates are metabolized to produce energy during rest or physical exercise. It is estimated using oxygen consumption (VO2) and carbon dioxide production (VCO2) measured through indirect calorimetry. CHOox is typically expressed in grams per minute (g/min).
Time frame: 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
This variable represents the amount of energy derived from fat and CHO oxidation during rest or exercise. It is estimated using oxygen consumption (VO2) and carbon dioxide production (VCO2) obtained through indirect calorimetry. Energy expenditure is typically expressed in kilocalories (kcal).
Time frame: 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
Lactate concentration represents the amount of lactate present in the blood during rest or exercise. It is measured using the Lactate Plus device through capillary puncture of the middle or ring finger of the non-dominant hand and is expressed in millimoles per liter (mmol/L). This variable provides information about anaerobic metabolism and exercise intensity.
Time frame: 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.
Resting Energy Expenditure (REE)
Resting energy expenditure refers to the amount of energy the body expends at rest to maintain essential physiological functions such as breathing, circulation, and cellular metabolism. It is typically measured using indirect calorimetry at rest and is commonly expressed in kilocalories per day (kcal/day).
Time frame: 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.
Power
Power will be assessed at different physiological stages during the exercise test, including submaximal and maximal intensities. Measurements are obtained using a cycle ergometer and expressed in watts (W). This variable provides insight into exercise capacity and performance at varying intensities.
Time frame: 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.
Maximal Oxygen Consumption (VO2máx)
Maximal oxygen consumption represents the highest rate at which oxygen can be taken up, transported, and utilized by the body during intense exercise. It is measured using indirect calorimetry during a graded exercise test and is expressed in milliliters of oxygen per kilogram of body weight per minute (mL/kg/min). VO2max reflects an individual's aerobic fitness and cardiorespiratory capacity.
Time frame: 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.
Ventilatory Volume (VE)
VE is the total volume of air inhaled and exhaled per minute. It is measured using indirect calorimetry and expressed in liters per minute (L/min). VE reflects ventilatory response during rest or exercise.
Time frame: 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.
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Oxygen Consumption (VO2)
VO2 is the volume of oxygen consumed per minute. It is measured using indirect calorimetry and expressed in mL/kg/min when adjusted for body weight.
Time frame: 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.
Carbon Dioxide Production (VCO2)
VCO2 is the volume of carbon dioxide produced per minute. It is measured via indirect calorimetry and expressed mL/kg/min when adjusted for body weight.
Time frame: 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.
Partial Pressure of Carbon Dioxide (PETCO2)
PETCO2 represents the partial pressure of carbon dioxide at the end of exhalation, measured using indirect calorimetry during exercise. It is expressed in millimeters of mercury (mmHg) and provides information about ventilatory efficiency, respiratory control, and gas exchange.
Time frame: 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.
Ventilatory Oxygen Equivalent (VE/VO2)
The ventilatory oxygen equivalent represents the ratio of minute ventilation (VE) to oxygen consumption (VO2). It is measured during rest or exercise using indirect calorimetry and expressed in liters of air per liter of O2 (L/L). VE/VO2 reflects ventilatory efficiency in relation to oxygen uptake.
Time frame: 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.
Ventilatory Carbon Dioxide Equivalent (VE/VCO2)
The ventilatory carbon dioxide equivalent represents the ratio of minute ventilation (VE) to carbon dioxide production (VCO2). It is measured during rest or exercise using indirect calorimetry and expressed in liters of air per liter of CO2 (L/L). VE/VCO2 indicates ventilatory efficiency in relation to carbon dioxide elimination.
Time frame: 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.
Heart Rate Variability (HRV)
HRV represents the variation in time intervals between consecutive heartbeats, reflecting autonomic nervous system activity. It is measured using a Polar H10 heart rate monitor and expressed in milliseconds (ms).
Time frame: 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.
Heart Rate (HR)
Heart rate represents the number of heartbeats per minute and reflects cardiovascular activity. It is typically measured using an electrocardiogram (ECG) or heart rate monitor and expressed in beats per minute (bpm).
Time frame: 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.
Oxygenated Haemoglobin (HbO2)
HbO2 represents the concentration of oxygen-bound hemoglobin in the blood or tissue. It is typically measured using near-infrared spectroscopy (NIRS) and expressed in micromoles (µM) or arbitrary units, reflecting tissue oxygenation levels.
Time frame: 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.
Deoxygenated Haemoglobin (HHb)
HHb represents the concentration of hemoglobin not bound to oxygen. Measured via NIRS, it provides information about oxygen extraction and utilization in the tissue and is expressed in µM or arbitrary units.
Time frame: 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.
% Tissue Saturation Index (%TSI)
Percentage of oxygen saturation in the microvascular tissue measured using a portable Near-Infrared Spectroscopy (NIRS) device. Reflects the balance between local oxygen delivery and utilization in muscle tissue.
Time frame: 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.
Body Mass Index (IMC)
BMI is a measure that relates a person's weight to their height to estimate body fatness. It is calculated as weight in kilograms divided by height in meters squared (kg/m2) and is commonly used to classify underweight, normal weight, overweight, and obesity. In this study, it was measured using bone densitometry with the Hologic Discovery QDR Wi.
Time frame: 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 Mass
Fat mass represents the total amount of body fat in an individual. It is measured using dual-energy X-ray absorptiometry (DEXA) and is expressed in kilograms (kg) or as a percentage of total body weight (%).
Time frame: 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.
Muscle Mass
Muscle mass represents the total weight of skeletal muscles in the body. It is measured using dual-energy X-ray absorptiometry (DEXA) and is expressed in kilograms (kg).
Time frame: 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.
Bone Mass
Bone mass represents the total weight of bone tissue in the body. It is measured using dual-energy X-ray absorptiometry (DEXA) and is expressed in kilograms (kg), providing information about bone health and density.
Time frame: 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.
Bone Mineral Density (BMD)
BMD represents the concentration of mineral content in a given area of bone, reflecting bone strength and health. It is typically measured using dual-energy X-ray absorptiometry (DEXA) and expressed in grams per square centimeter (g/cm2). BMD is commonly used to assess osteoporosis risk and bone quality.
Time frame: 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.
Total Visceral Fat Volume (cm3VAT)
Total visceral fat volume represents the amount of fat stored within the abdominal cavity surrounding internal organs. In this study, it is assessed using DXA (dual-energy X-ray absorptiometry) and expressed in cubic centimeters (cm³). This variable provides information on metabolic risk and cardiometabolic health.
Time frame: 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.
Basal Metabolic Rate (BMR; TMB in Spanish)
BMR represents the energy expenditure of the body at rest necessary to maintain essential physiological functions, such as breathing, circulation, and cellular metabolism. In this study, it is measured under standardized resting conditions through indirect calorimetry and expressed in kilocalories per day (kcal/day).
Time frame: 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.
Phase Angle (PhA)
Phase angle is a measure derived from bioelectrical impedance analysis (BIA) that reflects cell membrane integrity and overall cellular health. It is calculated from the relationship between resistance (R) and reactance (Xc) of body tissues and is expressed in degrees (°). Higher PhA values generally indicate better cellular function and body composition quality, while lower values may be associated with malnutrition or disease.
Time frame: 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.
Glucose
Glucose represents the concentration of sugar in the blood, which serves as the primary source of energy for the body's cells. It is measured using the Freestyle Optium Neo device with test strips and expressed in millimoles per liter (mmol/L). Blood glucose levels provide information about metabolic status, energy availability, and glycemic control.
Time frame: 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.
Lipid Profile
High-Density Lipoprotein Cholesterol (HDL), Low-Density Lipoprotein Cholesterol (LDL), Triglycerides (TG) and Total Cholesterol (TC), represent the concentrations of different types of fats and cholesterol in the blood. They are measured using the Afinion 2 device and expressed in millimoles per liter (mmol/L). Higher HDL levels are associated with lower cardiovascular risk, while elevated LDL, TG, and TC levels are linked to increased metabolic and cardiovascular risk.
Time frame: 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.
Glycated Hemoglobin (HbA1c)
HbA1c represents the percentage of hemoglobin that is glycated, reflecting the average blood glucose levels over the previous 2-3 months. In this study, HbA1c was measured using the Afinion 2 analyzer and is expressed as a percentage (%). It provides an indicator of long-term glycemic control.
Time frame: 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.
C-Reactive Protein (CRP)
CRP is a protein produced by the liver in response to inflammation, serving as a marker of systemic inflammatory status. In this study, CRP was measured using the Afinion 2 analyzer and is expressed in milligrams per liter (mg/L). It helps assess inflammatory processes and cardiovascular risk.
Time frame: 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.
Maximum Strenght
Maximum upper limb strength (SmaxUL), maximum right lower limb strength (SmaxRL), and maximum left lower limb strength (SmaxLL) represent the highest force generated by each respective limb during isometric strength tests. All measurements are conducted using a Kinvent dynamometer and are expressed in kilograms (kg). These variables reflect the maximal muscular capacity of the upper and lower limbs and allow for assessment of inter-limb strength and overall muscular performance.
Time frame: 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.
Maximum Upper Limb Strength Time (TSmaxUL)
Time required to reach maximal voluntary force during an upper limb isometric contraction measured with a K-Force Kinvent dynamometer. All measurements are conducted using a Kinvent dynamometer, with TSmaxUL values expressed in seconds (s), providing comprehensive information on muscle activation speed, explosive strength, and neuromuscular performance.
Time frame: 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.
Upper Limb Rate of Force Development (RFD_UL)
Speed at which force is generated during an upper limb contraction assessed using a K-Force Kinvent dynamometer. The RFD\_UL values are expressed in kilograms per second (Kg/s).
Time frame: 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.
Lower Limb Rate of Force Development (RFD_LL)
Speed at which force is produced during a lower limb contraction measured with a K-Force Kinvent dynamometer. The RFD\_LL values are expressed in kilograms per second (Kg/s).
Time frame: 1 week after diagnosis (baseline); 1 week after completion of neoadjuvant treatment; 4 weeks after breast surgery or surgeon approval; and 1 week after completion of the exercise intervention or control period.
Lower Limb Asymmetry (AsymLL)
Lower limb asymmetry (AsymLL) represents the difference in strength or force production between the right and left lower limbs during isometric or dynamic tests. It is calculated from measurements such as maximum lower limb strength or rate of force development and is typically expressed as a percentage (%). This variable provides insight into inter-limb imbalances, potential injury risk, and neuromuscular performance.
Time frame: 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.
Quality of Life (QLQ-C30)
Cancer-specific questionnaire that assesses health-related quality of life across multiple domains including physical, emotional, cognitive, and social functioning, as well as symptoms. It contains 30 items grouped into functional scales, symptom scales, and a global health status scale. Items are transformed to a 0-100 scale according to the EORTC scoring manual; higher scores indicate better functioning/global quality of life but greater symptom severity in symptom scales.
Time frame: 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.
Quality of life (QLQ-BR45)
Breast cancer-specific questionnaire designed to assess health-related quality of life, including symptoms, treatment side effects, body image, sexual functioning, and future perspective. It contains 45 items organized into functional and symptom scales. Items are transformed to a 0-100 scale following the EORTC scoring manual; higher scores indicate better functioning/global quality of life and higher symptom burden for symptom scales.
Time frame: 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.
Fatigue
Questionnaire designed to assess the impact of fatigue on physical performance and daily activities, evaluating perceived exertion, endurance, and functional limitations. Items are rated on Likert scales and summed or averaged according to the questionnaire instructions; higher scores indicate greater fatigue and reduced performance.
Time frame: 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.