An interventional study of Pre-habilitation exercise program in Breast Cancer, sponsored by University of Milan. Recruiting at 2 sites in Italy. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-08-20.
Sponsored by University of Milan · Not applicable, Interventional, and Treatment
PhActHealth is a multicenter randomized controlled trial enrolling women with newly diagnosed luminal B or triple-negative breast cancer (BC) who are candidates for neoadjuvant therapy. The study aims to investigate the effects of a preoperative, unsupervised exercise training program on exercise capacity, as well as on immune response, autonomic nervous system (ANS) regulation, cardiovascular health, and tumor aggressiveness prior to surgical removal.
Participants are randomly assigned to either an intervention group or a control group. All patients receive lifestyle counseling, while those in the intervention group additionally follow a personalized aerobic and resistance exercise program throughout the neoadjuvant treatment period before surgery.
The primary outcome is the improvement in exercise capacity. The secondary outcomes are tumor-specific and systemic responses to the intervention, evaluated by analyzing molecular, metabolic, and inflammatory markers, as well as clinical and functional parameters.
BC is strongly affected by systemic inflammation and immune alterations. Exercise has been demonstrated improving cardiometabolic health and reducing inflammatory markers in patients with oncology diseases. However, its role in the pre-operative setting, during neoadjuvant therapy, still remains poorly defined. The PhActHealth study investigates whether a structured pre-operative exercise program can improve functional capacity and modulate tumor and systemic biological markers in breast cancer patients, before surgery, and improve survival and quality of life, after surgery.
The PhActHealth study aims to comprehensively investigate the impact of a pre-operative, remotely monitored exercise training program in patients with BC, with a dual focus: (i) Improving exercise capacity; (ii) Exploring the potential modulation of biomarkers involved in tumor progression, systemic inflammation, and immune response by integrating functional assessments, biological analyses, and patient-reported outcomes.
Women with operable BC who are candidates for neoadjuvant therapy are enrolled after confirmation of eligibility criteria, and randomly assigned to either an intervention arm (IA) or a control arm (CA).
The intervention begins with the initiation of systemic therapy and continues until the planned date of surgery; then, two follow-ups are performed. At baseline, patients enrolled in both study arms receive lifestyle counseling, with specific recommendations for maintaining an active lifestyle based on the currently available international guidelines. In addition to lifestyle counseling, participants enrolled in the IA receive a personalized pre-habilitation exercise training program - which is undertaken autonomously and remotely monitored - until one week before surgery. Then, all participants undergo the planned surgical treatment, followed according to routine clinical practice, during which two follow-ups are scheduled.
The primary outcome is peak exercise capacity while secondary outcomes are tumor response and proliferation, immune and angiogenesis markers in tumor tissue, systemic inflammatory and metabolic biomarkers, body composition, autonomic function, and quality of life, overall and disease-free survival, as well as other functional and psychosocial parameters.
At baseline and before surgery, urine, blood, stool, and tumor biopsy samples are collected, and all primary and secondary outcomes are assessed, except overall and disease-free survival, which are assessed at the follow-up time-points, and quality of life which is assessed at all time-points.
14,825 studies on the registry are indexed under Breast Neoplasms; 3,319 are open to participants now.
This study's planned enrollment of 126 is above the median of 72 across 10,896 interventional studies indexed under Breast Neoplasms.
Browse Breast Neoplasms studies →University of Milan is the lead sponsor of 183 studies on the registry; 28 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HER2 is a protein, made from the ERBB2 gene, that drives the growth of some cancers. A study may look for a level of the protein, extra copies of the gene, or a particular change in it.
In breast cancer, protein tests are read as HER2-positive, HER2-low or HER2-negative; other cancers use their own rules. Check which test result the study requires.
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Chronic obstructive pulmonary disease: long-term lung disease that makes it hard to breathe out, including emphysema and chronic bronchitis.
HER2
HER2 is a protein, made from the ERBB2 gene, that drives the growth of some cancers. A study may look for a level of the protein, extra copies of the gene, or a particular change in it.
In breast cancer, protein tests are read as HER2-positive, HER2-low or HER2-negative; other cancers use their own rules. Check which test result the study requires.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Adjuvant and neoadjuvant
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
COPD
Chronic obstructive pulmonary disease: long-term lung disease that makes it hard to breathe out, including emphysema and chronic bronchitis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants receive specific recommendations for maintaining an active lifestyle, with additional guidance on nutritional habits, stress management, substance use, alcohol consumption, smoking, and sleep. Furthermore, participants are asked to wear a wrist-worn wearable device for the entire duration of the intervention in order to monitor their adherence to the intervention program: a 16-week personalized pre-habilitation exercise training, that includes a combination of aerobic endurance exercises, aimed at enhancing exercise capacity, and muscle-strengthening exercises, aimed at increasing muscle mass and strength.
Behavioral: Pre-habilitation exercise program
Participants receive specific recommendations for maintaining an active lifestyle, with additional guidance on nutritional habits, stress management, substance use, alcohol consumption, smoking, and sleep. Furthermore, participants are asked to wear a wrist-worn wearable device for the entire duration of the intervention in order to track physical activity habits.
Participants undertake a 16-week personalized pre-habilitation exercise training program as follows: * Aerobic training: five times per week with an initial session duration set at 45 minutes.The initial target intensity is set at 40% of the Heart Rate Reserve (HRR). Both duration and intensity are progressively increased based on individual exercise tolerance, aiming for an intensity of approximately 60% HRR and a duration of 60 minutes per session. * Resistance training: twice per week, ensuring at least 24-48 hours of recovery between sessions. Patients follow the prescribed number of sets and repetitions demonstrated in in the video tutorials provided by the study staff.
Exercise capacity
Change in metabolic equivalents of task (METs) at peak exercise intensity, measured during a maximal exercise stress test.
Time frame: Baseline and 6 months
Pathologic Complete Response (pCR)
Defined as the absence of residual invasive cancer in the breast and axillary lymph nodes at surgery (ypT0/is ypN0). Results will be reported as the proportion of participants achieving pCR (%)
Time frame: At surgery, following completion of neoadjuvant treatment
Residual Cancer Burden (RCB)
Assessed according to the validated RCB index calculated from primary tumor dimensions, tumor cellularity, and nodal involvement at surgery. Results will be reported as both continuous RCB score (unitless index) and categorical RCB class (RCB-0, RCB-I, RCB-II, RCB-III)
Time frame: At surgery, following completion of neoadjuvant treatment
Stromal Tumor-Infiltrating Lymphocytes (sTILs)
Assessed on hematoxylin and eosin (H\&E)-stained sections from diagnostic biopsies and surgical specimens according to the recommendations of the International Immuno-Oncology Biomarker Working Group. Results are reported as the percentage (%) the stromal area within the borders of the invasive tumor occupied by mononuclear inflammatory cells (predominantly lymphocytes and plasma cells).
Time frame: Baseline diagnostic biopsy and surgery
Tumor Angiogenesis
Assessed by immunohistochemical evaluation of tumor-associated microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression in tumor tissue. MVD is quantified using an endothelial marker such as CD31 or CD34 and reported as the number of immunostained microvessels per field or per mm². VEGF expression is reported as the percentage (%) of positive tumor cells and staining intensity.
Time frame: Baseline diagnostic biopsy and surgery
Tumor tissue Insulin-like growth factor 1 (IGF-1) expression
Evaluated by immunohistochemistry (IHC) and expressed as the percentage (%) of positive tumor cells in diagnostic biopsies and surgical specimens. Expression is quantified according to the percentage of positive tumor cells and staining intensity, using an H-score or an equivalent validated scoring system.
Time frame: Baseline diagnostic biopsy and surgery
IGF-1 receptor expression (IGF-1R)
Evaluated by immunohistochemistry (IHC) and measured as the percentage (%) of positive tumor cells staining intensity, and cellular localization, using an H-score or an equivalent validated scoring system.
Time frame: Baseline diagnostic biopsy and surgery
Ki-67 expression
Measured as the percentage (%) of positively stained tumor cells on diagnostic biopsies and surgical specimens. In hormone receptor-positive tumors, the proportion of patients achieving a post-treatment Ki-67 ≤2.7% will also be explored as an indicator of complete cell-cycle arrest. In TNBC, Ki-67 changes will be considered exploratory and interpreted together with pCR and RCB. In a subset of cases, transcript-level changes in proliferation- and immune-related genes will be explored using RNA in situ hybridization with spatial resolution.
Time frame: Baseline diagnostic biopsy and surgery
Lipid Profile
Change in total cholesterol (mg/dL), High-density lipoprotein (HDL) cholesterol (mg/dL), Low-density lipoprotein (LDL) cholesterol (mg/dL), triglycerides (mg/dL), assessed in the blood
Time frame: Baseline and 6 months
Blood glucose
Assessed in blood samples and expressed in milligrams per deciliter (mg/dL).
Time frame: Baseline and 6 months
Glycated hemoglobin (HbA1c)
Assessed in blood samples and expressed in millimoles per mole (mmol/mol)
Time frame: Baseline and 6 months
Insulin
Assessed in blood samples and expressed in milli-international units per liter (mIU/L).
Time frame: Baseline and 6 months
Liver function markers
Change in Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) assessed in the blood (U/L)
Time frame: Baseline and 6 months
C-reactive protein (CRP)
Change in C-reactive protein (CRP) (mg/dL), assessed in the blood
Time frame: Baseline and 6 months
High-sensitivity C-reactive protein (hs-CRP)
Change in High-sensitivity C-reactive protein (hs-CRP) (mg/dL), assessed in the blood
Time frame: Baseline and 6 months
Interleukin-6 (IL-6)
Change in Interleukin-6 (IL-6) (pg/mL), assessed in the blood
Time frame: Baseline and 6 months
Neutrophil-to-lymphocyte ratio (N/L)
Change in Neutrophil-to-lymphocyte ratio (N/L), calculated from blood neutrophil and lymphocyte counts
Time frame: Baseline and 6 months
Platelet-to-lymphocyte ratio (P/L)
Change in platelet-to-lymphocyte ratio (P/L), calculated from blood platelet and lymphocyte counts
Time frame: Baseline and 6 months
Thyroid Function
Change in Thyroid-stimulating hormone (TSH) assessed in the blood (mIU/L)
Time frame: Baseline and 6 months
Epigenetic markers
Changes in DNA methylation and miRNA expression will be assessed using validated molecular techniques. DNA methylation will be evaluated by genome-wide methylation arrays and/or bisulfite pyrosequencing, while miRNA expression will be quantified by reverse transcription quantitative PCR (RT-qPCR).
Time frame: Baseline and post-intervention/pre-surgery
Gut microbiota
Change in microbial diversity (species diversity %) assessed by next-generation sequencing (NGS) of the V3-V4 region of the 16S rDNA gene
Time frame: At follow up (6 and 12 months)
Body mass index (BMI)
Calculated as body mass in kilograms (kg) divided by height in meters squared (m²) and is expressed in kilograms per square meter (kg/m²).
Time frame: Baseline and 6 months
Fat Mass (FM)
Assessed by bioimpedance analysis (BIA 101, Akern, Italy, BodyStat Ltd.) and is expressed as a percentage (%).
Time frame: Baseline and 6 months
Fat-free mass (FFM)
Assessed by bioimpedance analysis (BIA 101, Akern, Italy, BodyStat Ltd.) and is expressed as a percentage (%).
Time frame: Baseline and 6 months
Total body water (TBW)
Assessed by bioimpedance analysis (BIA 101, Akern, Italy, BodyStat Ltd.) and is expressed as a percentage (%).
Time frame: Baseline and 6 months
Heart rate variability (HRV)
Change in heart rate variability (HRV), assessed by noninvasive autoregressive spectral analysis of continuously recorded 2-lead electrocardiographic signals using the CubeStress System (configuration package HD+12), at rest and during active orthostatism.
Time frame: Baseline and 6 months
Blood pressure variability (BPV)
Change in blood pressure variability (BPV), assessed by noninvasive autoregressive spectral analysis of continuously recorded blood pressure signals using the CubeStress System (configuration package HD+12), at rest and during active orthostatism.
Time frame: Baseline and 6 months
Respiratory Frequency
Change in respiratory frequency, assessed from continuously recorded respiratory signals using a piezoelectric respiratory band placed on the chest and connected to the CubeStress System (configuration package HD+12), at rest and during active orthostatism.
Time frame: Baseline and 6 months
Physical Activity
Change in physical activity level assessed using the International Physical Activity Questionnaire (IPAQ), administered as part of the lifestyle questionnaire.
Time frame: Baseline and 6 months
Dietary Habits
Change in adherence to a healthy dietary pattern assessed using the American Heart Association Healthy Diet Score (AHA score), administered as part of the lifestyle questionnaire.
Time frame: Baseline and 6 months
Final compliance questionnaire
A custom-made questionnaire evaluating the subjective perception of the effects of exercise
Time frame: At 6 months
Health-related quality of life
Assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). The questionnaire includes functional scales (physical, role, cognitive, emotional, and social functioning), symptom scales (fatigue, pain, nausea, and vomiting), and a global health status/quality of life scale. Scores are transformed to a 0-100 scale. Higher scores indicate better quality of life.
Time frame: Baseline, 6 months and at follow ups at 6 and 12 months
Mental health
Assessed using Mental Health Continuum Short Form (MHC-SF), composed of 14 items. Each item can be scored between 0 and 5 and the total score on the scale can range from 0 to 70 points. Higher scores indicate a higher level of emotional wellbeing.
Time frame: Baseline and 6 months
Anxiety and depression
Assessed using the Hospital Anxiety and Depression Scale (HADS), a 14-item questionnaire comprising two 7-item subscales measuring anxiety (HADS-A) and depression (HADS-D). Each item is scored on a 4-point Likert scale (0-3). Subscale scores range from 0 to 21, with higher scores indicating greater anxiety or depressive symptoms.
Time frame: Baseline and 6 months
Daily sleepiness
Assessed using the Epworth Sleepiness Scale (ESS), an 8-item self-administered questionnaire. Each item is rated on a 4-point scale (0-3), and the total score ranges from 0 to 24. Higher scores indicate a greater likelihood of dozing or falling asleep.
Time frame: Baseline and 6 months
Quality of sleep
Assessed using the Pittsburgh Sleep Quality Index (PSQI), a 19-item questionnaire comprising seven component scores that are summed to generate a global score ranging from 0 to 21. Higher scores indicate poorer sleep quality.
Time frame: Baseline and 6 months
6-Minute Walking Test (6MWT)
Performed according to international guidelines to assess aerobic capacity. The total distance walked during the 6-minute test is recorded in meters (m).
Time frame: Baseline and 6 months
Handgrip strength (HGS) - Right Hand
Assessed using an isometric dynamometer to evaluate upper limb muscle strength. The assessment is performed in a sitting position with the elbow flexed at 90 degrees. Three measurements are performed, with each measurement recorded in kilograms (kg). The mean of the three readings is calculated as the final right-hand handgrip strength value, expressed in kilograms (kg).
Time frame: Baseline and 6 months
Handgrip strength (HGS) - Left Hand
Assessed using an isometric dynamometer to evaluate upper limb muscle strength. The assessment is performed in a sitting position with the elbow flexed at 90 degrees. Three measurements are performed, with each measurement recorded in kilograms (kg). The mean of the three readings is calculated as the final left-hand handgrip strength value, expressed in kilograms (kg).
Time frame: Baseline and 6 months
Plan to share: No
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Started Feb 2026 (actual). Primary completion is estimated for Feb 2028, 24 months after the start.
Of 2,661 non-industry interventional studies with no phase under Breast Neoplasms, half reached primary completion within 33 months of starting (the median), counting those still running; a quarter within 16 and three quarters within 66. This study's planned 24 months is below that.
Counting every sponsor, half of 2,771 studies reached it within 33 months; a quarter within 15 and three quarters within 66.
How these figures are worked out, and which studies are left out of them.
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