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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
SINGLE
Enrollment
55
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).
Latvian Biomedical Research and Study centre
Riga, Select One, Latvia
Miller-Payne grade
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.
Time frame: 6 months
Gene expression profile
Alterations in the tumor gene expression profile will be assessed by RNA sequencing of surgical tumor and normal breast tissue specimens
Time frame: 12 months
RNA cargo of extracellular vesicles
Exercise-induced alterations in the RNA cargo of circulating extracellular vesicles will be studied by RNA sequencing
Time frame: Before intervention and after 6 months
Protein cargo of extracellular vesicles
Exercise-induced alterations in the protein cargo of circulating extracellular vesicles will be studied by proteomic analysis
Time frame: Before intervention and after 6 months
Number and phenotype of tumor-infiltrating immune cells
Immunophenotyping of tumor-infiltrating immune cells will be performed by multiplex immunofluorescence in breast tumor tissue specimens
Time frame: 12 months
Global health-related quality of life
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.
Time frame: 6 months
Breast cancer-related quality of life
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.
Time frame: 6 months
VO2 peak
Oxygen peak consumption will be measured by UNCCRI treadmill protocol
Time frame: Before intervention and after 6 months
30 sec sit-to-stand test
The number of sit- and stand-up movement repetitions achieved during 30 sec will be recorded
Time frame: Before intervention and after 6 months
6-minute walk test
The test will be performed indoors on 30 m long testing course and length of walked distance will be measured
Time frame: Before intervention and after 6 months
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