Breast Cancer
Conditions
Keywords
High intensity interval training
Brief summary
The goal of this clinical trial is to learn how regular physical exercise affects breast cancer patients' response to standard neoadjuvant chemotherapy (NAC) and to gain an insight into the molecular mechanisms underlying the effects of exercise on cancer biology. of exercise-induced alterations in cancer gene expression and the immune tumor microenvironment. The main questions it aims to answer are: * Does a high-intensity interval training (HIIT) program during treatment improve patients' response to NAC and quality of life as compared to low level of physical activity during the treatment? * What are the differences in the residual tumor gene expression and tumor infiltrating immune cell profile between patients taking HIIT during the NAC and patients with low level of physical activity? * What are the roles of extracellular vesicles (EVs) in mediating the effects of exercise on cancer progression? Patients in HIIT group will undergo a personalized HIIT program consisting of 3 training sessions per week for the whole duration of NAC, whereas patients from the control group (Ctrl) will be advised to maintain their usual level of physical activity during NAC. After the breast surgery, response to NAC will be assessed by Miller-Payne grading. Tumor and normal breast tissue specimens will be collected for RNA sequencing analysis. Blood samples will be collected before and immediately after the training for the analysis of RNA and protein cargo of circulating EVs.
Interventions
BEHAVIORALHigh-intensiy interval training
All participants undergo physical capacity tests before the onset of NAC and after the last course of NAC but before the breast cancer surgery. A treadmill protocol consisting of twenty-one 1-minute stages, with speed and/or grade increments at each stage, is used to obtain VO2 peak (the highest amount of oxygen consumed at peak exercise) data. The HIIT intervention consists of 2 to 3 exercise sessions per week for 6 months. The HIIT session starts with a 6-minute warm-up period at about 65-70% of maximal heart rate (HRmax) followed by 4 X 4-min high-intensity intervals (85%-95% of HRmax) combined with 3 min period of active recovery (55-70% of HRmax).
Sponsors
Riga East Clinical University Hospital
Latvian Academy of Sport Education
Latvian Biomedical Research and Study Centre
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
30 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Primary breast cancer; stage IIA-B, IIIA-C (TNM: T1-4, N0-3, M0) at diagnosis * Diagnosis established by core needle biopsy * Age 30-65 years * Prescribed doxorubicin/cyclophosphamide-based NAC * Oral and written consent
Exclusion criteria
* Cardiac pathologies * Pregnancy * Blood transfusion in the last six months * Another oncological disease * Previous chemotherapy, hormonal or X-ray treatment * Participation in another clinical trial * Currently performing more than 180 min of moderate to high intensity aerobic training per week
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Miller-Payne grade | 6 months | Response to NAC assessed by histological examination of residual tumor at surgery using Miller-Payne grading from 1 to 5, where grade 1 means no response or some alterations to individual malignant cells but no reduction in overall cellularity, whereas grade 5 is a pathological complete response. |
| Gene expression profile | 12 months | Alterations in the tumor gene expression profile will be assessed by RNA sequencing of surgical tumor and normal breast tissue specimens |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number and phenotype of tumor-infiltrating immune cells | 12 months | Immunophenotyping of tumor-infiltrating immune cells will be performed by multiplex immunofluorescence in breast tumor tissue specimens |
| Global health-related quality of life | 6 months | Global health-related quality of life will be assessed by the European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30). All scales and single-item measures yield scores ranging from 0 to 100. A high score on a functional scale indicates superior functioning and a high score on the global health status/QoL scale indicates a high quality of life. Conversely, a high score on a symptom scale or item indicates a heightened level of health complaints and/ or presence of treatment side effects. |
| Breast cancer-related quality of life | 6 months | Breast cancer-related quality of life assessed by the European Organisation for Research and Treatment of Cancer Breast cancer module (EORTC QLQ-B23) questionnaire that includes 23 questions addressing disease symptoms, treatment side effects, body image, sexual functioning, and future perspectives. All scales and single-item measures yield scores ranging from 0 to 100. |
| RNA cargo of extracellular vesicles | Before intervention and after 6 months | Exercise-induced alterations in the RNA cargo of circulating extracellular vesicles will be studied by RNA sequencing |
| 30 sec sit-to-stand test | Before intervention and after 6 months | The number of sit- and stand-up movement repetitions achieved during 30 sec will be recorded |
| 6-minute walk test | Before intervention and after 6 months | The test will be performed indoors on 30 m long testing course and length of walked distance will be measured |
| VO2 peak | Before intervention and after 6 months | Oxygen peak consumption will be measured by UNCCRI treadmill protocol |
| Protein cargo of extracellular vesicles | Before intervention and after 6 months | Exercise-induced alterations in the protein cargo of circulating extracellular vesicles will be studied by proteomic analysis |
Countries
Latvia
Outcome results
None listed