Radiation Therapy in Treating Women Who Have Undergone Surgery for Early-Stage Invasive Breast Cancer

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Radiation to the tumor site and surrounding area may kill more tumor cells. It is not yet known if radiation therapy to the breast alone following surgery is more effective than radiation therapy to the breast plus surrounding tissue in treating invasive breast cancer. PURPOSE: This randomized phase III trial is studying radiation therapy to the breast alone to see how well it works compared to radiation therapy to the breast plus surrounding tissue in treating women who have undergone surgery for early-stage invasive breast cancer.

Detailed Description
-----------------
OBJECTIVES: Compare the overall survival, disease-free survival, isolated local regional disease-free survival, and distant disease-free survival in women with previously resected, early stage, invasive breast cancer treated with breast radiotherapy with or without regional radiotherapy. Compare the toxic effects of these regimens in these patients. Compare the quality of life of patients (in certain participating centers) treated with these regimens. Compare the cosmetic outcomes in patients (in certain participating centers) treated with these regimens. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to number of positive nodes (0 vs 1-3 vs more than 3), number of axillary nodes removed (<10, > or equal to 10); type of chemotherapy (anthracycline containing vs other vs none), hormonal therapy (yes vs no), number of axillary lymph nodes excised*, and participating center. Patients are randomized to one of two treatment arms. NOTE: * Patients with a negative sentinel node dissection with or without an axillary dissection will be stratified according to the total number of nodes removed Arm I: Patients undergo standard breast radiotherapy alone 5 days a week for 5 weeks in the absence of disease progression or unacceptable toxicity. Arm II: Patients undergo breast and regional radiotherapy 5 days a week for 5 weeks in the absence of disease progression or unacceptable toxicity. Radiotherapy in both arms begins as soon as possible after randomization. Radiotherapy must begin within 8 weeks after completion of adjuvant IV chemotherapy, unless radiotherapy is administered concurrently with chemotherapy (i.e., cyclophosphamide, methotrexate, and fluorouracil [CMF]), or within 16 weeks after the last breast surgery for patients treated with hormonal therapy alone. Quality of life is assessed (in patients in certain participating centers) within 2 weeks prior to randomization, during the last week of radiotherapy, at 3 and 9 months after completion of radiotherapy, and then annually until first distant disease recurrence. Cosmetic outcome is assessed (in patients in certain participating centers) within 2 weeks prior to randomization, and then at 3 and 5 years after completion of radiotherapy or until first distant disease recurrence. Patients are followed at 3, 6, and 9 months, every 6 months for 2 years, and then annually thereafter. PROJECTED ACCRUAL: Approximately 1,822 patients will be accrued for this study within approximately 4 years.

Official Title
-----------------
A Phase III Study of Regional Radiation Therapy in Early Breast Cancer

Conditions
-----------------
Breast Cancer

Intervention / Treatment
-----------------
* Radiation: Standard Breast Irradiation
* Radiation: Breast Radiation plus Regional Radiation


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically proven invasive carcinoma of the breast No evidence of T4, N2-3, or M1 disease prior to surgery Node positive or high-risk node negative Prior breast-conserving therapy (BCT) (e.g., lumpectomy, partial mastectomy, or segmental mastectomy) and axillary node dissection or sentinel node biopsy required and must be a candidate for breast radiotherapy after BCT Normally patients should have microscopically clear resection margins and those with positive margins should undergo reexcision Patients with microscopically focally positive margins (defined as no greater than 3 times high power fields) are candidates for breast radiotherapy plus a boost to the lumpectomy site Patients with prior sentinel node dissection eligible if node negative, but still meet high-risk criteria If node positive, then a level I and II axillary dissection must be performed No evidence of residual disease in axilla after dissection Must be treated with currently accepted adjuvant systemic chemotherapy and/or hormonal therapy High risk of regional and systemic recurrence due to one of the following: Pathologically positive axillary lymph nodes Pathologically negative axillary lymph nodes with one of the following: Primary tumor greater than 5 cm Primary tumor greater than 2 cm and less than 10 axillary lymph nodes excised and one of the following: Estrogen receptor negative Skarf-Bloom-Richardson grade 3 Lymphovascular invasion Hormone receptor status: Estrogen and progesterone receptor status known PATIENT CHARACTERISTICS: Age: 16 and over Sex: Female Menopausal status: Premenopausal or postmenopausal Performance status: ECOG 0-2 Life expectancy: At least 5 years Hematopoietic: Not specified Hepatic: SGOT and/or SGPT no greater than 3 times upper limit of normal (ULN)* Alkaline phosphatase no greater than 3 times ULN* NOTE: * Patients with laboratory values greater than 3 times ULN may still be eligible if no metastatic disease by imaging examinations Renal: No serious nonmalignant renal disease Cardiovascular: No serious nonmalignant cardiovascular disease Pulmonary: No serious nonmalignant pulmonary disease Other: Not pregnant or nursing Fertile patients must use effective contraception No other serious nonmalignant disease (e.g., systemic lupus erythematosus or scleroderma) that would preclude definitive surgery or radiotherapy No other malignancy except: Nonmelanomatous skin cancer Carcinoma in situ of the cervix or endometrium Contralateral noninvasive breast cancer (unless prior radiotherapy to the contralateral breast) Invasive carcinoma of the cervix, endometrium, colon, thyroid, or melanoma that was curatively treated at least 5 years prior to study participation No psychiatric or addictive disorder that would preclude informed consent or study compliance PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: See Disease Characteristics Concurrent standard adjuvant chemotherapy allowed Endocrine therapy: See Disease Characteristics Concurrent standard adjuvant hormonal therapy allowed Radiotherapy: See Disease Characteristics Surgery: See Disease Characteristics

Ages Eligible for Study
-----------------
Minimum Age: 16 Years
Maximum Age: 120 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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: Standard Breast Irradiation<br> | Radiation: Standard Breast Irradiation<br>* Standard Breast Irradiation - A dose of 5000 cGy in 25 fractions at a rate of 200 cGy per day, 5 days a week for 5 weeks will be prescribed to the standard tangent fields.<br>|
| Experimental: Breast Radiation plus regional radiation<br>regional radiation therapy (to the ipsilateral supraclavicular, axillary and internal mammary nodes) | Radiation: Breast Radiation plus Regional Radiation<br>* Breast Radiation plus Regional Radiation - A dose of 5000 cGy in 25 fractions at a rate of 200 cGy per day, 5 days a week for 5 weeks will be prescribed to the modified wide tangent fields.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Duration of study | 10 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free Survival | Disease-free survival (including locoregional and distant disease) | 10 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
stage I breast cancer, stage II breast cancer