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

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.

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