Radiation Therapy in Women With Low Risk Early-Stage Breast Cancer Who Have Undergone Breast Conservation Surgery

Study Overview
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Brief Summary
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RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Giving radiation therapy after surgery may kill any tumor cells that remain after surgery. It is not yet known whether intensity-modulated radiation therapy is more effective than standard radiation therapy in treating patients with early-stage breast cancer. PURPOSE: This randomized phase III trial is comparing radiation therapy regimens in treating women with early-stage breast cancer who have undergone breast-conservation surgery.

Detailed Description
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OBJECTIVES: To test partial breast radiotherapy using intensity-modulated techniques following complete local tumor excision in women with low-risk, early stage breast cancer. OUTLINE: This is a multicenter study. Patients are stratified according to center (not participating in sub-studies vs participating in sub-studies). Patients are randomized to 1 of 3 treatment arms. Arm I (control): Patients undergo standard whole breast radiotherapy once daily on days 1-5 (15 fractions) for 3 weeks. Arm II: Patients undergo reduced whole breast radiotherapy (15 fractions) and standard partial breast radiotherapy (15 fractions) once daily on days 1-5 for 3 weeks. Arm III: Patients undergo standard partial breast radiotherapy once daily on days 1-5 (15 fractions) for 3 weeks. All patients complete a family history questionnaire at baseline. Patients also undergo blood sample collection at baseline and paraffin-embedded tissue collection at follow-up for molecular studies analyzing inter-patient variation by microarrays. Patients in centers participating in sub-studies undergo quality of life and health economic assessment at baseline, 6 months, and 1, 2, and 5 years. These patients also undergo photographic assessment at baseline, 2 years, and 5 years. After completion of study treatment, patients are followed for 10 years.

Official Title
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Randomised Trial Testing Intensity Modulated and Partial Organ Radiotherapy After Breast Conservation Surgery for Early Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of low-risk early stage breast cancer, meeting the following criteria: Invasive adenocarcinoma No invasive carcinoma of classical lobular type lympho-vascular invasion present or absent Tumor size pathologically determined to be ≤ 3.0 cm in diameter (pT1-2) (< 3.1 cm maximum microscopic diameter of invasive component) Unifocal disease Grade I, II, or III disease Axillary lymph nodes negative or 1-3 nodes positive (pN0 or pN+(1-3)) Must have undergone breast conservation surgery with or without adjuvant systemic therapy Minimum microscopic margin of non-cancerous tissue ≥ 2 mm (excluding deep margin if this is at deep fascia) At low risk of local recurrence after radiotherapy (< 1% annual risk local recurrence) No prior mastectomy No blood-borne metastases PATIENT CHARACTERISTICS: No prior malignancy except nonmelanoma skin cancer PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior endocrine therapy or chemotherapy Neoadjuvant endocrine therapy allowed provided the tumour is < 3.0 cm and all other inclusion criteria are met No primary endocrine therapy as a replacement for surgery No concurrent chemoradiotherapy

Ages Eligible for Study
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Minimum Age: 50 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm I (control)<br>Patients undergo standard whole breast radiotherapy once daily on days 1-5 for 3 weeks. | Radiation: radiation therapy<br>* Patients undergo standard whole breast, reduced whole breast, or standard partial breast radiotherapy<br>|
| Experimental: Arm II<br>Patients undergo reduced whole breast radiotherapy and standard partial breast radiotherapy once daily on days 1-5 for 3 weeks. | Radiation: radiation therapy<br>* Patients undergo standard whole breast, reduced whole breast, or standard partial breast radiotherapy<br>|
| Experimental: Arm III<br>Patients undergo standard partial breast radiotherapy once daily on days 1-5 for 3 weeks. | Radiation: radiation therapy<br>* Patients undergo standard whole breast, reduced whole breast, or standard partial breast radiotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local tumor control in the ipsilateral breast (i.e., true recurrence plus new primary tumor) as confirmed by cytological or histological assessment |  | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Location of tumor relapse |  | 5 years | 
| Contralateral primary breast cancer or other primary tumors as confirmed by cytological or histological assessment |  | 5 years | 
| Regional and distant metastases |  | 5 years | 
| Late adverse effects in normal tissue normal tissues as determined periodically by photographic assessments (in a subset of patients), physician assessments, and patient self-assessments |  | 5 years | 
| Quality of life as assessed by EORTC QLQ C-30, EORTC QLQ-BR23, BIS, and HADS questionnaires in a subset of patients at baseline, 6 months, and 1, 2, and 5 years |  | 5 years | 
| Cost-effectiveness as assessed by EQ-5D questionnaire at baseline, 6 months, and 1, 2, and 5 years |  | 10 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent breast cancer, stage IA breast cancer, stage II breast cancer, invasive ductal breast carcinoma, invasive ductal breast carcinoma with predominant intraductal component