Triple-Negative Breast Cancer (TNBC)NCT07484776
Metabolic Flexibility in Patients With Early Triple-negative Breast Cancer
A study testing Cardiovascular training at maximal fat oxidation (FATmax), Cardiovascular training at maximal aerobic power (MAP) and Resistance training in people with Triple-Negative Breast Cancer (TNBC), run by Universidad Europea de Madrid at 1 site in Spain.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 20 to 55 years, women only
- Conditions the study is for
- Triple-Negative Breast Cancer (TNBC)
- What is being tested?
- Cardiovascular training at maximal fat oxidation (FATmax), Cardiovascular training at maximal aerobic power (MAP) and Resistance training
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteSpain
- Study dates
- 10 Feb 2026to 25 Mar 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 55 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Female between 20-55 years of age.
- Confirmed histological new diagnosis of stage I to III triple-negative breast cancer and a candidate to receive systemic neoadjuvant treatment with chemotherapy +/- immunotherapy.
- Must not have started systemic treatment for the neoplastic disease.
- Participating in any external physical exercise program or sports activities during the experimental study phase.
- Inability to understand and provide written Informed Consent (IC)
Who cannot join
- Having neurological or orthopedic disease at the time of recruitment or during the study evaluation and intervention.
- Inability to understand Spanish language.
- Presenting absolute contraindications for performing a cardiopulmonary exercise test (CPET) such as heart failure, myocarditis, acute pericarditis, severe aortic stenosis, aortic dissection, vascular toxicity, uncontrolled severe arterial hypertension, uncontrolled severe cardiac arrhythmias, pulmonary thromboembolism, or severe anemia.
- Have relative contraindications for performing a CPET such as bradyarrhythmias or tachyarrhythmias, moderate valvular stenosis, inability to perform physical or mental exertion, chronic infectious diseases, musculoskeletal disabilities, ventricular aneurysm, second- or third-degree atrioventricular block, or severe arterial hypertension.
Trial locations and contacts
1 site in 1 country.
Spain1 site
Universidad Europea de Madrid, Villaviciosa de Odón
Madrid, Madrid, 28670
About this study
Official title: Metabolic Flexibility in Patients With Early Triple-negative Breast Cancer and the Possible Effect of a Physical Exercise Intervention
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).
Read more
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.
Read the detailed description
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.
- Conditions
- Triple-Negative Breast Cancer (TNBC)
- Being tested
- Cardiovascular training at maximal fat oxidation (FATmax), Cardiovascular training at maximal aerobic power (MAP), Resistance training
- Keywords
- Triple-Negative Breast Cancer, Metabolic Flexibility, Mitocondrial disfunction, Maximal Fat Oxidation, Exercise Intervention, Cardiovascular Training, Resistance Training
- Medical subject headings
- Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cardiovascular training at maximal fat oxidation (FATmax)Other
Group performing cardiovascular training at maximal fat oxidation (FATmax) twice per week for 12 weeks
Cardiovascular training at maximal aerobic power (MAP)Other
Group performing cardiovascular training at maximal aerobic power (MAP) twice per week for 12 weeks
Resistance trainingOther
Group performing progressive resistance training twice per week for 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| Control group | No intervention | Receives the general physical activity recommendations from the WHO |
| Cardiovascular training group at maximal fat oxidation (FATmax) | Experimental | Group performing cardiovascular training at maximal fat oxidation (FATmax) through continuous training on a stationary bicycle at a low-to-moderate intensity. There will be a progressive increase in the number of minutes throughout the intervention. Receives: Other: Cardiovascular training at maximal fat oxidation (FATmax) |
| Cardiovascular training group at maximal aerobic power (MAP) | Experimental | Group performing cardiovascular training at maximal aerobic power (MAP) through high-intensity interval training on a stationary bicycle. There will be a progressive increase in the minutes performed at MAP throughout the intervention Receives: Other: Cardiovascular training at maximal aerobic power (MAP) |
| Resistance training group | Experimental | Participants in resistance training group will follow a 12-week strength training program with progressive loads, twice a week. The intervention in this group will be based on the key training principles in the field of health: the principle of individualization, the principle of supercompensation, and the principle of specificity.
There will be a two-week familiarization period that will take into account the patient's initial level, starting with moderate loads to reach high loads up to 1 repetition in reserve (RIR 1) by the end of the intervention. Receives: Other: Resistance training |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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.
Measured: 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.
Secondary outcomes (34)
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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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 (%).
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2026
- Study start10 Feb 2026
- Primary completion25 Mar 2027 (estimated)
- Study completion25 Mar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (76)Papers the sponsor has linked to this study.
- Other trials for Triple-Negative Breast Cancer (TNBC)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Universidad Europea de Madrid
- Sponsor type
- University, hospital or other
- Collaborators
- European University of Madrid, Hospital Severo Ochoa, Hospital Universitario Infanta Leonor, Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
- Responsible party
- Principal investigator, Lidia Brea Alejo, European University of Madrid
- Investigators
- Brea Lidia, Profesor titular UEM, Principal investigator, Universidad Europea de Madrid
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07484776
- Sponsor's protocol ID
- 2025-712
- Status last verified
- Mar 2026
- First submitted
- 27 Feb 2026
- Last updated
- 20 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Williams MA, Haskell WL, Ades PA, Amsterdam EA, Bittner V, Franklin BA, Gulanick M, Laing ST, Stewart KJ; American Heart Association Council on Clinical Cardiology; American Heart Association Council on Nutrition, Physical Activity, and Metabolism. Resistance exercise in individuals with and without cardiovascular disease: 2007 update: a scientific statement from the American Heart Association Council on Clinical Cardiology and Council on Nutrition, Physical Activity, and Metabolism. Circulation. 2007 Jul 31;116(5):572-84. doi: 10.1161/CIRCULATIONAHA.107.185214. Epub 2007 Jul 16.
PubMed 17638929Thompson PD, Arena R, Riebe D, Pescatello LS; American College of Sports Medicine. ACSM's new preparticipation health screening recommendations from ACSM's guidelines for exercise testing and prescription, ninth edition. Curr Sports Med Rep. 2013 Jul-Aug;12(4):215-7. doi: 10.1249/JSR.0b013e31829a68cf. No abstract available.
PubMed 23851406Paulo AC, Forjaz CLM, Mion D Jr, Silva GV, Barros S, Tricoli V. Blood Pressure Increase in Hypertensive Individuals During Resistance Training Protocols With Equated Work to Rest Ratio. Front Physiol. 2020 Jun 29;11:481. doi: 10.3389/fphys.2020.00481. eCollection 2020.
PubMed 32714194Fletcher GF, Balady GJ, Amsterdam EA, Chaitman B, Eckel R, Fleg J, Froelicher VF, Leon AS, Pina IL, Rodney R, Simons-Morton DA, Williams MA, Bazzarre T. Exercise standards for testing and training: a statement for healthcare professionals from the American Heart Association. Circulation. 2001 Oct 2;104(14):1694-740. doi: 10.1161/hc3901.095960. No abstract available.
PubMed 11581152Davis SN, Tate D, Hedrington MS. Mechanisms of hypoglycemia and exercise-associated autonomic dysfunction. Trans Am Clin Climatol Assoc. 2014;125:281-91; discussion 291-2.
PubMed 25125745Dupuy O, Douzi W, Theurot D, Bosquet L, Dugue B. An Evidence-Based Approach for Choosing Post-exercise Recovery Techniques to Reduce Markers of Muscle Damage, Soreness, Fatigue, and Inflammation: A Systematic Review With Meta-Analysis. Front Physiol. 2018 Apr 26;9:403. doi: 10.3389/fphys.2018.00403. eCollection 2018.
PubMed 29755363Myers J, Arena R, Franklin B, Pina I, Kraus WE, McInnis K, Balady GJ; American Heart Association Committee on Exercise, Cardiac Rehabilitation, and Prevention of the Council on Clinical Cardiology, the Council on Nutrition, Physical Activity, and Metabolism, and the Council on Cardiovascular Nursing. Recommendations for clinical exercise laboratories: a scientific statement from the american heart association. Circulation. 2009 Jun 23;119(24):3144-61. doi: 10.1161/CIRCULATIONAHA.109.192520. Epub 2009 Jun 1. No abstract available.
PubMed 19487589Riebe D, Franklin BA, Thompson PD, Garber CE, Whitfield GP, Magal M, Pescatello LS. Updating ACSM's Recommendations for Exercise Preparticipation Health Screening. Med Sci Sports Exerc. 2015 Nov;47(11):2473-9. doi: 10.1249/MSS.0000000000000664.
PubMed 26473759Kambic T, Hansen D, Eijsvogels TMH. High-load resistance training in cardiac rehabilitation: is it time to debunk old clinical dogmas for a better clinical tomorrow? Eur J Prev Cardiol. 2024 Sep 6;31(12):e92-e94. doi: 10.1093/eurjpc/zwae079. No abstract available.
PubMed 38394775Ferreira IC, Souza MA, Junior MA, Silveira-Nunes G, Barbosa MA, Barbosa AC. Validity of a portable hanging scale to assess the isometric muscle strength during knee movement. J Bodyw Mov Ther. 2021 Oct;28:433-438. doi: 10.1016/j.jbmt.2021.06.004. Epub 2021 Jun 24.
PubMed 34776175Olds M, McLaine S, Magni N. Validity and Reliability of the Kinvent Handheld Dynamometer in the Athletic Shoulder Test. J Sport Rehabil. 2023 Jun 7;32(7):764-772. doi: 10.1123/jsr.2022-0444. Print 2023 Sep 1.
PubMed 37290770Akinyemiju T, Oyekunle T, Salako O, Gupta A, Alatise O, Ogun G, Adeniyi A, Deveaux A, Hall A, Ayandipo O, Olajide T, Olasehinde O, Arowolo O, Adisa A, Afuwape O, Olusanya A, Adegoke A, Tollefsbol TO, Arnett D, Muehlbauer MJ, Newgard CB; H3 Africa Kidney Research Network; Daramola A. Metabolic Syndrome and Risk of Breast Cancer by Molecular Subtype: Analysis of the MEND Study. Clin Breast Cancer. 2022 Jun;22(4):e463-e472. doi: 10.1016/j.clbc.2021.11.004. Epub 2021 Nov 23.
PubMed 34980540Howard FM, Olopade OI. Epidemiology of Triple-Negative Breast Cancer: A Review. Cancer J. 2021 Jan-Feb 01;27(1):8-16. doi: 10.1097/PPO.0000000000000500.
PubMed 33475288Karim AM, Eun Kwon J, Ali T, Jang J, Ullah I, Lee YG, Park DW, Park J, Jeang JW, Kang SC. Triple-negative breast cancer: epidemiology, molecular mechanisms, and modern vaccine-based treatment strategies. Biochem Pharmacol. 2023 Jun;212:115545. doi: 10.1016/j.bcp.2023.115545. Epub 2023 Apr 11.
PubMed 37044296Delsoglio M, Dupertuis YM, Oshima T, van der Plas M, Pichard C. Evaluation of the accuracy and precision of a new generation indirect calorimeter in canopy dilution mode. Clin Nutr. 2020 Jun;39(6):1927-1934. doi: 10.1016/j.clnu.2019.08.017. Epub 2019 Sep 10.
PubMed 31543335
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Metabolic Flexibility in Patients With Early Triple-negative Breast Cancer and the Possible Effect of a Physical Exercise Intervention
- ClinicalTrials.gov ID
- NCT07484776
- Acronym / sponsor ID
- 2025-712
- Conditions
- Triple-Negative Breast Cancer (TNBC)
- Keywords
- Triple-Negative Breast Cancer, Metabolic Flexibility, Mitocondrial disfunction, Maximal Fat Oxidation, Exercise Intervention, Cardiovascular Training, Resistance Training
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Universidad Europea de MadridUniversity, hospital or other
- Collaborators
- European University of Madrid, Hospital Severo Ochoa, Hospital Universitario Infanta Leonor, Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
- Study start
- 10 Feb 2026 (actual)
- Primary completion
- 25 Mar 2027 (estimated)
- Study completion
- 25 Mar 2028 (estimated)
- First posted
- 20 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Control group | No intervention | –Receives the general physical activity recommendations from the WHO |
| Cardiovascular training group at maximal fat oxidation (FATmax) | Experimental | Other: Cardiovascular training at maximal fat oxidation (FATmax)Group performing cardiovascular training at maximal fat oxidation (FATmax) through continuous training on a stationary bicycle at a low-to-moderate intensity. There will be a progressive increase in the number of minutes throughout the intervention. |
| Cardiovascular training group at maximal aerobic power (MAP) | Experimental | Other: Cardiovascular training at maximal aerobic power (MAP)Group performing cardiovascular training at maximal aerobic power (MAP) through high-intensity interval training on a stationary bicycle. There will be a progressive increase in the minutes performed at MAP throughout the intervention |
| Resistance training group | Experimental | Other: Resistance trainingParticipants in resistance training group will follow a 12-week strength training program with progressive loads, twice a week. The intervention in this group will be based on the key training principles in the field of health: the principle of individualization, the principle of supercompensation, and the principle of specificity. There will be a two-week familiarization period that will take into account the patient's initial level, starting with moderate loads to reach high loads up to 1 repetition in reserve (RIR 1) by the end of the intervention. |
Who may qualify
- Ages
- 20 to 55 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Female between 20-55 years of age.
- Confirmed histological new diagnosis of stage I to III triple-negative breast cancer and a candidate to receive systemic neoadjuvant treatment with chemotherapy +/- immunotherapy.
- Must not have started systemic treatment for the neoplastic disease.
- Participating in any external physical exercise program or sports activities during the experimental study phase.
- Inability to understand and provide written Informed Consent (IC)
Key exclusion criteria (4 listed)
- Having neurological or orthopedic disease at the time of recruitment or during the study evaluation and intervention.
- Inability to understand Spanish language.
- Presenting absolute contraindications for performing a cardiopulmonary exercise test (CPET) such as heart failure, myocarditis, acute pericarditis, severe aortic stenosis, aortic dissection, vascular toxicity, uncontrolled severe arterial hypertension, uncontrolled severe cardiac arrhythmias, pulmonary thromboembolism, or severe anemia.
- Have relative contraindications for performing a CPET such as bradyarrhythmias or tachyarrhythmias, moderate valvular stenosis, inability to perform physical or mental exertion, chronic infectious diseases, musculoskeletal disabilities, ventricular aneurysm, second- or third-degree atrioventricular block, or severe arterial hypertension.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cardiovascular training at maximal fat oxidation (FATmax)Group performing cardiovascular training at maximal fat oxidation (FATmax) twice per week for 12 weeks | Other | Cardiovascular training group at maximal fat oxidation (FATmax) |
| Cardiovascular training at maximal aerobic power (MAP)Group performing cardiovascular training at maximal aerobic power (MAP) twice per week for 12 weeks | Other | Cardiovascular training group at maximal aerobic power (MAP) |
| Resistance trainingGroup performing progressive resistance training twice per week for 12 weeks | Other | Resistance training group |
Primary outcome
Respiratory Exchange Ratio (RER)
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.
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).
Fat Oxidation (FATox)
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 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).
Carbohydrate Oxidation (CHOox)
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 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).
Energy Expenditure
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.
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).
Lactate Concentration
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 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.
34 secondary outcomes
Resting Energy Expenditure (REE)
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
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)
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)
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.
Oxygen Consumption (VO2)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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
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
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
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)
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)
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)
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)
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
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
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)
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)
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
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 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)
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)
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)
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)
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)
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
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2026.
- Background: PubMed 17638929Williams MA, Haskell WL, Ades PA, Amsterdam EA, Bittner V, Franklin BA, Gulanick M, Laing ST, Stewart KJ; American Heart Association Council on Clinical Cardiology; American Heart Association Council on Nutrition, Physical Activity, and Metabolism. Resistance exercise in individuals with and without cardiovascular disease: 2007 update: a scientific statement from the American Heart Association Council on Clinical Cardiology and Council on Nutrition, Physical Activity, and Metabolism. Circulation. 2007 Jul 31;116(5):572-84. doi: 10.1161/CIRCULATIONAHA.107.185214. Epub 2007 Jul 16.
- Background: PubMed 23851406Thompson PD, Arena R, Riebe D, Pescatello LS; American College of Sports Medicine. ACSM's new preparticipation health screening recommendations from ACSM's guidelines for exercise testing and prescription, ninth edition. Curr Sports Med Rep. 2013 Jul-Aug;12(4):215-7. doi: 10.1249/JSR.0b013e31829a68cf. No abstract available.
- Background: PubMed 32714194Paulo AC, Forjaz CLM, Mion D Jr, Silva GV, Barros S, Tricoli V. Blood Pressure Increase in Hypertensive Individuals During Resistance Training Protocols With Equated Work to Rest Ratio. Front Physiol. 2020 Jun 29;11:481. doi: 10.3389/fphys.2020.00481. eCollection 2020.
- Background: PubMed 11581152Fletcher GF, Balady GJ, Amsterdam EA, Chaitman B, Eckel R, Fleg J, Froelicher VF, Leon AS, Pina IL, Rodney R, Simons-Morton DA, Williams MA, Bazzarre T. Exercise standards for testing and training: a statement for healthcare professionals from the American Heart Association. Circulation. 2001 Oct 2;104(14):1694-740. doi: 10.1161/hc3901.095960. No abstract available.
- Background: PubMed 25125745Davis SN, Tate D, Hedrington MS. Mechanisms of hypoglycemia and exercise-associated autonomic dysfunction. Trans Am Clin Climatol Assoc. 2014;125:281-91; discussion 291-2.
- Background: PubMed 29755363Dupuy O, Douzi W, Theurot D, Bosquet L, Dugue B. An Evidence-Based Approach for Choosing Post-exercise Recovery Techniques to Reduce Markers of Muscle Damage, Soreness, Fatigue, and Inflammation: A Systematic Review With Meta-Analysis. Front Physiol. 2018 Apr 26;9:403. doi: 10.3389/fphys.2018.00403. eCollection 2018.
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- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brea Lidia, Profesor titular UEM principal investigator
Universidad Europea de Madrid
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cardiovascular training at maximal fat oxidation (FATmax), Cardiovascular training at maximal aerobic power (MAP) and Resistance training in people with Triple-Negative Breast Cancer (TNBC), run by Universidad Europea de Madrid at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 20 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Respiratory Exchange Ratio (RER) (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.). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07484776, which also lists 76 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2026; AzTrials last refreshed its copy on 7 Nov 2026.