Effects of Physical Exercise on Response to Treatement in Breast Cancer
NCT Number: NCT06522971
Acronym: CancerBeat
Status: ACTIVE_NOT_RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Breast Cancer
Interventions: BEHAVIORAL: High-intensiy interval training
Sponsor: Latvian Biomedical Research and Study Centre
Collaborators: Riga East Clinical University Hospital|Latvian Academy of Sport Education
Sex: FEMALE
Age: ADULT, OLDER_ADULT
Enrollment: 55
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: SINGLE (OUTCOMES_ASSESSOR)|Primary Purpose: BASIC_SCIENCE
Start Date: 2022-08-16
Completion Date: 2025-12
Locations: Latvian Biomedical Research and Study centre, Riga, Select One, LV1067, Latvia

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.

Primary Outcome Measures: 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., 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, 12 months
Secondary Outcome Measures: RNA cargo of extracellular vesicles, Exercise-induced alterations in the RNA cargo of circulating extracellular vesicles will be studied by RNA sequencing, 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, 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, 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., 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., 6 months|VO2 peak, Oxygen peak consumption will be measured by UNCCRI treadmill protocol, 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, 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, Before intervention and after 6 months