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

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 in different ways may kill any tumor cells that remain after surgery. It is not yet known whether whole breast radiation therapy is more effective than partial breast radiation therapy in treating breast cancer. PURPOSE: This randomized phase III trial is studying whole breast radiation therapy to see how well it works compared to partial breast radiation therapy in treating women who have undergone surgery for ductal carcinoma in situ or stage I or stage II breast cancer.

Detailed Description
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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.

Official Title
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A Randomized Phase III Study of Conventional Whole Breast Irradiation (WBI) Versus Partial Breast Irradiation (PBI) for Women With Stage 0, I, or II Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Radiation: 3-dimensional conformal accelerated partial breast irradiation
* Radiation: brachytherapy
* Radiation: whole breast irradiation
* Radiation: MammoSite or other single-entry intracavitary device


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 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: Group 1: WBI<br>Patients undergo whole breast irradiation (WBI) once daily, 5 days a week for 5-7 weeks. | Radiation: whole breast irradiation<br>* Patients undergo radiation therapy once daily (days 1-5) for up to 7 weeks<br>|
| Experimental: Group 2: PBI<br>Patients undergo partial-breast irradiation (PBI) twice daily on 5 days over a period of 5-10 days. This may be delivered by intracavitary brachytherapy, MammoSite or other single-entry intracavitary device, or 3-dimensional conformal accelerated partial breast irradiation. | Radiation: 3-dimensional conformal accelerated partial breast irradiation<br> <br> Radiation: brachytherapy<br> <br> Radiation: MammoSite or other single-entry intracavitary device<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| In-breast tumor recurrence (IBTR) |  | every 6 months for 5 years; annually thereafter for up to 10 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | time from randomization to death due to any cause assessed up to 15 years | 
| Recurrence-free survival |  | time from randomization to recurrence assessed every 6 months for 5 years and annually thereafter for up to 10 years | 
| Distant disease-free survival |  | time from randomization to event occurrence assessed every 6 months for 5 years and annually thereafter for up to 10 years | 
| Quality of life and patient-reported cosmesis by Breast Cancer Treatment Outcome Scale, MOS SF-36 Vitality, Convenience of Care scale, and symptoms |  | measured at baseline, and 1 and 6 months and 1, 2, and 3 years after completion of study treatment | 
| Toxicity as assessed by adverse events during treatment |  | at end of RT, and 4 weeks, 6 months, 12 months; every 6 months for years 2 through 5; and annually thereafter for up to 10 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage II breast cancer, ductal breast carcinoma in situ, breast cancer in situ, stage IA breast cancer, stage IB breast cancer