Breast Cancer Early Stage Breast Cancer (Stage 1-3), Breast Neoplasm Malignant Female
Conditions
Keywords
breast cancer, sarcopenia, neoadjuvant chemotherapy, exercise, resistance training, body composition, physical activity, quality of life, skeletal muscle, pathologic complete response, relative dose intensity
Brief summary
The goal of this clinical trial is to learn whether supervised exercise is practical and safe for women receiving chemotherapy before surgery for breast cancer. The main questions it aims to answer are: * Can participants attend and complete the supervised exercise program during chemotherapy? * Is the exercise program safe? * Does exercise help maintain muscle mass, strength, quality of life, and chemotherapy delivery? Participants will be assigned to either: * supervised aerobic and strength exercise during chemotherapy, or * usual care without a study exercise program. Researchers will compare the two groups before and after chemotherapy.
Interventions
OTHERSupervised exercise
Supervised combined aerobic and resistance exercise during neoadjuvant chemotherapy, delivered as two supervised sessions per week throughout the course of NACT.
Sponsors
King Hamad University Hospital, Bahrain
Bahrain Oncology Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologically confirmed invasive breast carcinoma, clinical stage I-III. 2. Female, age ≥18 years. 3. Planned to undergo standard neoadjuvant chemotherapy of ≥4 months duration with curative intent, followed by definitive surgery. This includes common regimens such as taxane- and anthracycline-based chemotherapy or TCHP (docetaxel, carboplatin, trastuzumab, pertuzumab) for HER2-positive disease. 4. Availability of a baseline CT or PET/CT scan (as part of routine diagnosis or staging) that includes axial images at the third lumbar vertebra (L3) level, performed prior to starting NACT. 5. Anticipated post-NACT CT or PET/CT scan (e.g. for re-staging) that includes the L3 level, to be performed after completion of NACT and before surgery per standard care practice. 6. Eastern Cooperative Oncology Group (ECOG) performance status 0-2. 7. Cleared by treating oncologist and physiotherapist as medically able to participate in a moderate-intensity exercise program (e.g. able to walk independently with or without an assistive device and perform basic resistance exercises). 8. Able and willing to provide written informed consent. 9. Able to understand study instructions and complete questionnaires.
Exclusion criteria
1. Evidence of distant metastatic disease (stage IV) or treatment plan not aiming for curative intent. 2. Unstable or severe cardiac, pulmonary, or other systemic comorbidities that would make moderate exercise unsafe, such as unstable angina or recent myocardial infarction, decompensated heart failure, uncontrolled severe arrhythmia, uncontrolled severe hypertension, or severe symptomatic lung disease. 3. Major musculoskeletal or neurological conditions that would preclude safe participation in supervised exercise (e.g. unstable orthopedic injuries, severe neuropathy or neurologic deficit, or recent major surgery not yet recovered). 4. Current second active malignancy (excluding second localized early breast cancer). 5. Regular participation in ≥150 minutes per week of moderate-vigorous aerobic activity and ≥2 resistance training sessions per week in the 3 months before cancer diagnosis. 6. Baseline imaging not available or not including L3, or patient unlikely to have a post-NACT scan including L3 (e.g. if they refuse imaging). 7. CT images of insufficient quality (e.g. severe artifacts or truncated field of view at L3) that would prevent accurate muscle measurement. 8. Pregnant or breastfeeding at the time of enrollment. 9. Significant cognitive impairment, psychiatric disorder, or language barrier that would prevent informed consent or compliance with the protocol. 10. Any other condition or circumstance that, in the opinion of the investigator, would make participation not in the patient's best interest or would compromise the scientific integrity of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility of exercise intervention during neoadjuvant chemotherapy | From initiation of the supervised exercise program through completion of neoadjuvant chemotherapy. The exercise program will continue throughout the full course of neoadjuvant chemotherapy, approximately 4-6 months depending on the treatment regimen. | Exercise adherence will be assessed in the exercise arm using physiotherapist-maintained session logs. Adherence is defined as attendance at ≥65% of prescribed supervised sessions during NACT, calculated as (sessions attended / sessions prescribed) × 100%. Prescribed sessions are the supervised sessions scheduled for the participant from randomization until completion of NACT or withdrawal from the study, whichever occurs first. The intervention will be considered feasible if at least 50% of participants randomized to the exercise arm meet the adherence threshold. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CT-derived body composition | SMI and SFI will be assessed at two time points: at baseline (pre-NACT) and at completion of NACT, which is expected to occur approximately 4-6 months after initiation of NACT and prior to surgery (post-NACT). | Skeletal muscle index (SMI) and subcutaneous fat index (SFI) will be measured on routine baseline and post-NACT computerized tomography (CT) images. SMI is defined as the cross-sectional area of skeletal muscle at the third lumbar vertebra (L3) on CT (in square centimeters) normalized for height (meters squared), yielding units of cm²/m². SFI is defined as the cross-sectional area of subcutaneous fat at the third lumbar vertebra (L3) on CT (in square centimeters) normalized for height (meters squared), yielding units of cm²/m². |
| Pathologic Complete Response (pCR) | Within one month after surgery. | pCR is defined as the absence of residual invasive cancer in the resected breast specimen and lymph nodes following NACT (allowing for residual in situ carcinoma), commonly denoted ypT0/Tis, ypN0. pCR will be determined based on the post-surgical pathology report. |
| European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Scores: | At baseline (pre-NACT) and at completion of NACT, which is expected to occur approximately 4-6 months after initiation of NACT and prior to surgery (post-NACT). | Quality of life will be measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, version 3 (EORTC QLQ-C30). Scores for each scale range from 0 to 100. Higher scores on the global health status and functioning scales indicate better health or functioning, while higher scores on the symptom scales indicate greater symptom severity. |
| European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Breast Cancer Module 23 Scores: | At baseline (pre-NACT) and at completion of NACT, which is expected to occur approximately 4-6 months after initiation of NACT and prior to surgery (post-NACT). | Breast cancer-specific quality of life will be measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Breast Cancer Module 23 (EORTC QLQ-BR23). Scores for each scale range from 0 to 100. Higher scores on the functioning scales indicate better functioning, while higher scores on the symptom scales indicate greater symptom severity. |
| Muscle strength | Grip strength will be measured at baseline (pre-NACT) and at completion of NACT, which is expected to occur approximately 4-6 months after initiation of NACT and prior to surgery (post-NACT). | Grip (in kg) strength will be assessed using handgrip dynamometry. |
| Safety and adverse events | From initiation of NACT through completion of NACT, approximately 4-6 months. | Safety will be evaluated by tracking adverse events (AEs) and serious adverse events (SAEs) throughout the study, particularly any events related to the exercise intervention. All participants will be assessed at each clinical visit for adverse events, and exercise session logs will also capture any symptoms or events during or after exercise. |
| Chemotherapy Delivery and Dose Intensity | From initiation through completion of NACT, approximately 4-6 months. | Relative Dose Intensity (RDI): RDI is defined as the delivered dose intensity (mg/m²/week for each cytotoxic drug) expressed as a percentage of the planned dose intensity. Dose reductions: Any reduction in chemotherapy dose below the initially planned dose (for reasons other than weight change) will be recorded. Cycle delays: Any delay of a chemotherapy cycle by ≥7 days from the intended date (for toxicity or other patient factors) will be recorded. Early discontinuation: If a patient permanently discontinues NACT before completing the planned number of cycles (due to toxicity, patient choice, etc.), that will be noted. |
| Radiologic response | After completion of NACT and prior to surgery, approximately 4-6 months after initiation of NACT. | Tumor response on imaging will be assessed by RECIST 1.1 criteria on post-NACT scans. |
Countries
Bahrain
Contacts
CONTACTZeki G Surmeli
Outcome results
None listed