Radiation Therapy (WBI Versus PBI) in Treating Women Who Have Undergone Surgery For Ductal Carcinoma In Situ or Stage I or Stage II Breast Cancer

OBJECTIVES:

Primary

• Compare local tumor control in women with ductal carcinoma in situ or stage I or II breast cancer treated with adjuvant whole breast vs partial breast irradiation following lumpectomy.

Secondary

• Compare overall survival, recurrence-free survival, and distant disease-free survival in patients treated with these regimens.
• Compare the cosmetic result in patients treated with these regimens.
• Compare fatigue and treatment-related symptoms in patients treated with these regimens.
• Compare perceived convenience of care in patients treated with these regimens.
• Compare acute and late toxic effects of these regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to disease stage (ductal carcinoma in situ [DCIS] only vs invasive and node negative vs invasive with 1-3 positive nodes), menopausal status (premenopausal vs postmenopausal), hormone receptor status (estrogen receptor [ER]-positive and/or progesterone receptor [PR]-positive vs ER-negative and PR-negative), intention to receive chemotherapy (yes vs no). Patients are randomized to 1 of 2 treatment arms. (Patients who are 50 years of age and over with DCIS regardless of hormone receptor status AND patients with invasive breast cancer meeting all of the following criteria: ≥ 50 years of age, node-negative, and hormone-receptor positive status will not be enrolled in study after 12/30/2006.)

• Group 1: Patients undergo whole-breast irradiation (WBI) once daily, 5 days a week, for 5-7 weeks.
• Group 2: Patients undergo partial-breast irradiation (PBI) twice daily on 5 days over a period of 5-10 days. This may be delivered by multi-catheter brachytherapy, single-entry intracavitary brachytherapy, or 3-D conformal radiotherapy.

Patients in both arms may receive adjuvant chemotherapy at least 2 weeks prior to initiation of WBI OR at least 2 weeks after completion of PBI at the discretion of the treating physician. Patients with ER-positive or PR-positive tumors may also receive hormonal therapy, beginning 3-12 weeks after completion of adjuvant chemotherapy (or before, during, or after completion of WBI or PBI for patients not receiving adjuvant chemotherapy) and continuing for at least 5 years.

After completion of study treatment, patients are followed at 1 and 6 months, every 6 months for 4.5 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 4,300 patients (2,150 per treatment arm) will be accrued for this study within 4.6 years. Note: Accrual closed on April 16, 2013, following approval of the Data Monitoring Committee to reduce the sample size from 4,300 to 4,214 patients.

DISEASE CHARACTERISTICS:

• Histologically confirmed ductal carcinoma in situ (DCIS*) or invasive* adenocarcinoma of the breast

• Stage 0, I, or II disease

• Stage II tumors must be ≤ 3 cm
• Gross disease must be unifocal

• Microscopic multifocality allowed provided total pathological tumor size is ≤ 3 cm
• No proven multicentric carcinoma in more than 1 quadrant or separated by ≥ 4 cm
• No non-epithelial breast malignancies (e.g., sarcoma or lymphoma) NOTE: *Patients who are 50 years of age and over with DCIS regardless of hormone receptor status AND patients with invasive breast cancer meeting all of the following criteria: ≥ 50 years of age, node-negative, and hormone-receptor positive status will not be enrolled in study after 12/30/2006
• Prior axillary staging required for patients with invasive breast cancer, including 1 of the following:

• Sentinel node biopsy alone (if sentinel node is negative)
• Sentinel node biopsy followed by axillary dissection or sampling with ≥ 6 axillary nodes (if sentinel node is positive)
• Axillary dissection alone with ≥ 6 axillary nodes
• No more than 3 positive axillary nodes

• No axillary nodes with definite evidence of microscopic or macroscopic extracapsular extension
• No positive non-axillary sentinel nodes (intramammary nodes are staged as axillary nodes)
• No palpable or radiographically suspicious ipsilateral or contralateral axillary, supraclavicular, infraclavicular, or internal mammary nodes unless there is histologic confirmation that these nodes are negative for tumor
• Must have undergone lumpectomy

• Resected margins histologically free of tumor
• Re-excision of surgical margins allowed
• Target lumpectomy cavity clearly delineated AND target lumpectomy/whole breast reference volume ≤ 30% based on postoperative pre-randomization CT scan
• Final surgery (i.e., lumpectomy, re-excision of margins, or axillary staging procedure) within the past 42 days
• No suspicious microcalcifications, densities, or palpable abnormalities in the ipsilateral or contralateral breast unless biopsied and found to be benign
• No Paget's disease of the nipple
• No history of invasive breast cancer or DCIS

• Prior lobular carcinoma in situ treated by surgery alone allowed
• No synchronous bilateral invasive or non-invasive breast cancer
• Partial breast irradiation deemed technically deliverable by radiation oncologist at a credentialed facility
• Must have undergone a history and physical exam within the past 4 months AND a bilateral mammogram within the past 6 months
• Hormone receptor status:

• Estrogen receptor (ER) status known
• Progesterone status known if ER analysis is negative
• Marginal or borderline results are considered positive

PATIENT CHARACTERISTICS:

Age

• 18 and over

Sex

• Female

Menopausal status

• Premenopausal or postmenopausal

Performance status

• Not specified

Life expectancy

• At least 10 years, excluding diagnosis of breast cancer

Hematopoietic

• Not specified

Hepatic

• Not specified

Renal

• Not specified

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective non-hormonal contraception
• No other malignancy within the past 5 years except previously treated carcinoma in situ of the cervix or colon, melanoma in situ, or basal cell or squamous cell skin cancer

• Deemed to be at low risk for recurrence
• No collagen vascular disease (e.g., systemic lupus erythematosus or scleroderma), specifically dermatomyositis with a creatine phosphokinase (CPK) level above normal, or active skin rash
• No psychiatric or addictive disorder that would preclude study therapy

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior biologic therapy for this malignancy

Chemotherapy

• No prior chemotherapy for this malignancy
• No concurrent chemotherapy during study radiotherapy

Endocrine therapy

• No prior hormonal therapy for this malignancy unless total duration of hormonal therapy was no more than 28 days before randomization
• Concurrent hormonal therapy allowed provided it is not administered during chemotherapy
• No concurrent raloxifene, tamoxifen, or other selective estrogen receptor modulating drugs
• No concurrent hormone replacement therapy
• No concurrent Femring^®

Radiotherapy

• No prior radiotherapy for this malignancy
• No prior breast or thoracic radiotherapy
• No concurrent brachytherapy boosts
• No concurrent intensity modulated radiotherapy
• No concurrent regional nodal irradiation

Surgery

• See Disease Characteristics
• No prior breast implants

• Patients who have had implants removed are eligible

Other

• No other concurrent anticancer therapy