Breast Cancer
Conditions
Keywords
Protein turnover, Skeletal muscle deconditoning, Breast cancer, Chemotherapy, Muscle biopsy
Brief summary
This study aims to investigate the acute effects (i.e. 4 days) of paclitaxel or paclitaxel vs trastuzumab or paclitaxel and carboplatine on skeletal muscle of breast cancer patients. Muscle biopsies will be performed, as well as measurements of body composition strength, muscle architecture and quality of life.
Detailed description
Breast cancer patients are commonly treated with chemotherapy, which is known to induce severe side effects such as skeletal muscle deconditioning, characterized by skeletal muscle atrophy and major mitochondrial alterations. These maladaptations, observed in patients treated with epirubicin-cyclophosphamide (EC) followed by weekly paclitaxel (TAX), ultimately lead to reduction in exercise capacity and quality of life. However, little is known about the specific effect of each type of chemotherapy. In our recent article (see Citations field in the References module), The investigators demonstrated that chemotherapy effects on skeletal muscle are drug-dependent. Using muscle biopsies before and 4 days after the first administration of EC or TAX, we demonstrated that unlike TAX, EC induced severe muscle atrophy and mitochondrial alterations. Of note, patients in the TAX group had already received EC during the preceding weeks (Figure 1). Therefore, these patients had already begun to have altered skeletal muscle homeostasis, which might have limited the influence of TAX compared with that of its administration in isolation (i.e., without other previous chemotherapy administrations). In addition, some patients had received, concomitantly with TAX, Trastuzumab (TRASTU) due to HER tumor mutation. Also, in triple negative breast cancers, the recommendations concerning neo(adjuvant) chemotherapy have recently changed and recommend starting treatment with the use of paclitaxel + carboplatin (TAX + CARBO).
Interventions
OTHERFirst Assessment
pre-treatment assessment
OTHERSecond Assessment
4 days post-treatment assessment
Sponsors
Institut de cancérologie Strasbourg Europe
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
TAX group : * Female ≥ 18 years * Stage I to III breast cancer * Patient who has not yet started treatment with TAX * Enrolled in a social security scheme * Able to speak, read and understand French TAX+TRASTU group : * Female ≥ 18 years of age * Stage I to III breast cancer * Patient who has not yet started treatment with TAX+TRASTU (Tolaney regimen) * Enrolled in a social security scheme * Able to speak, read and understand French
Exclusion criteria
* Prior exposure to chemotherapy * Musculoskeletal disorders, autoimmune, vascular or neuromuscular disease * Implantation of a pacemaker * Contraindications to fitness evaluation * Contraindication to local anesthesia for microbiopsy * Minor or protected adult * Pregnant women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To investigate the effects of a chemotherapy session on mitochondrial function of skeletal muscle in breast cancer patients by comparing the first session of TAX to the first session of TAX + TRASTU or +CARBO. | Change at 4 days post-treatment compare to baseline | difference of a score combining the mitochondrial respiratory capacity with production of hydrogen peroxide, difference in protein levels (western blots) and mRNA (RT-qPCR) expression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Compare the effect of the first TAX to the first TAX+TRASTU or +CARBO on muscle fiber cross-sectional area;cellular mechanisms of inflammation,fat infiltration and protein turnover;body composition;strength;muscle architecture and quality of life | Change at 4 days post-treatment compare to baseline | difference of a score combining the mitochondrial respiratory capacity with production of hydrogen peroxide, difference in protein levels (western blots) and mRNA (RT-qPCR) expression. |
Countries
France
Outcome results
None listed