Acute Effects of Chemotherapy Administration on Skeletal Muscle of Breast Cancer Patients: the PROTECT-06 Study

Study Overview
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Brief Summary
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Chemotherapy treatments such as epirubicin-cyclophosphamid or paclitaxel lead to severe off-target side effects such as skeletal muscle deconditioning. To date, three different studies investigated skeletal muscle decontioning in breast cancer patients, through long term protocols including all chemotherapy cycle treatment, and highlighted both structural alterations and impaired cellular processes. However, no study is currently availbale on the acute effect of one single chemotherapy administration in breast cancer patients skeletal muscle tissue. Our study is therefore dedicated to the investigation of the acute effect of the first dose administration of both Epuribicin/cyclophosphamide and Paclitaxel chemotherapies on skeletal muscle of breast cancer patients.

Detailed Description
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Chemotherapy treatments such as epirubicin-cyclophosphamid or paclitaxel lead to severe off-target side effects such as skeletal muscle deconditioning. Resulting from a global perturbation of the muscle homeostasis, skeletal muscle is characterized by both structural and functional alterations that will translate into a decrease in muscle mass and/or force as well as an increase in muscle fatigability. These maladaptations result in a reduced quality of life and an increased treatment-related toxicity, ultimately leading to an increased mortality risk.To date, three different studies investigated skeletal muscle decontioning in breast cancer patients, through long term protocols including all chemotherapy cycle treatment, and highlighted both structural alterations and impaired cellular processes. However, no study is currently availbale on the acute effect of one single chemotherapy administration in breast cancer patients skeletal muscle tissue.Our study is therefore dedicated to the investigation of the acute effect of the first dose administration of both Epuribicin/cyclophosphamide and Paclitaxel chemotherapies on skeletal muscle of breast cancer patients. Our study will particularly explore cellular mechanisms of muscle decontioning, such as protein turnover, mitochondrial homeostasis and fatty infiltrations.

Official Title
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Acute Effects of Chemotherapy Administration on Skeletal Muscle of Breast Cancer Patients: the PROTECT-06 Study

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Epirubicin-cyclophosphamide
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Breast cancer (stade I to III) Patient recieving the first administration of epirubicin-cyclophosphamide (group 1) or paclitaxel (group 2) for early breast cancer treatment Exclusion Criteria: History of cancer Known chronic pathology Pacemaker Contraindication to the evaluation of the physical condition Contraindication to the local anesthesia for the muscle micro-biopsy Breastfeeding or pregnant woman

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Epirubicin-cyclophosphamide<br>Woman with early breast cancer receiving a first cycle of epirubicin-cyclphosphamide | Drug: Epirubicin-cyclophosphamide<br>* 1 cycle of Epirubicin-cyclophosphamide<br>* Other names: Epirubicin-endoxan;|
| Paclitaxel<br>Woman with early breast cancer receiving a first cycle of paclitaxel | Drug: Paclitaxel<br>* 1 cycle of Paclitaxel<br>* Other names: Taxol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigate the acute effect of chemotherapy administration on protein turnover cellular processes through vastus lateralis biopsies of breast cancer patients | Change From Baseline in Western Blots measurements of protein expression levels | Before and 4 days after the chemotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigate the acute effect of chemotherapy administration on structural alterations | Change From Baseline in Cross-Sectional Area (CSA) measurements | Before and 4 days after the chemotherapy | 
| Investigate the acute effect of chemotherapy administration on inflammation | Change From Baseline in Western Blots measurments of protein expression levels | Before and 4 days after the chemotherapy | 
| Investigate the acute effect of chemotherapy administration on mitochondrial homeostasis | Change From Baseline in Western Blot measurement of protein expression levels | Before and 4 days after the chemotherapy | 
| Investigate the acute effect of chemotherapy administration on fatty infiltrations | Change From Baseline in Western Blot measurement of protein expression levels | Before and 4 days after the chemotherapy | 
| Investigate the acute effect of chemotherapy administration on satellite cells | Change From Baseline in Western Blot measurement of protein expression levels | Before and 4 days after the chemotherapy | 
| .Comparison of the acute effect of Epirubicin-Cyclophosphamide versus Paclitaxel on the skeletal muscle mass | Change From Baseline in quantity of muscle mass measured by bioelectrical impedance analysis | Before and 4 days after the chemotherapy | 
| Comparison of the acute effect of Epirubicin-Cyclophosphamide versus Paclitaxel on the muscle force | Change From Baseline in the maximal isometric strength of the knee with force transducer | Before and 4 days after the chemotherapy | 
| Comparison of the acute effect of Epirubicin-Cyclophosphamide versus Paclitaxel on the muscle thickness | Change From Baseline in ultrasonography measurement | Before and 4 days after the chemotherapy | 
| Comparison of the acute effect of Epirubicin-Cyclophosphamide versus Paclitaxel on the muscle fibers angle of pennation | Change From Baseline in ultrasonography measurement | Before and 4 days after the chemotherapy | 
| Comparison of the acute effect of Epirubicin-Cyclophosphamide versus Paclitaxel on the muscle fibers fascicle length | Change From Baseline in ultrasonography measurement | Before and 4 days after the chemotherapy | 
| Comparison of the acute effect of Epirubicin-Cyclophosphamide versus Paclitaxel on the echogenecity | Change From Baseline in ultrasonography measurement | Before and 4 days after the chemotherapy | 
| Comparison of the acute effect of Epirubicin-Cyclophosphamide versus Paclitaxel on the quality of life | Change From Baseline in FACT-G auto-questionnaire measurement | Before and 4 days after the chemotherapy | 
| Comparison of the acute effect of Epirubicin-Cyclophosphamide versus Paclitaxel on the appetite loss | Change From Baseline in FAACT auto-questionnaire measurement | Before and 4 days after the chemotherapy | 
| Comparison of the acute effect of Epirubicin-Cyclophosphamide versus Paclitaxel on the physical activity level | Change From Baseline in GPAQ auto-questionnaire measurement | Before and 4 days after the chemotherapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Protein turnover, Skeletal muscle deconditoning, Breast cancer, Chemotherapy, Muscle biopsy