Radiation Therapy With or Without Optional Tamoxifen in Treating Women With Ductal Carcinoma in Situ

Study Overview
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Brief Summary
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RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using tamoxifen may fight breast cancer by blocking the uptake of estrogen by the tumor cells. It is not yet known if radiation therapy is more effective than observation, with or without tamoxifen, in treating ductal carcinoma in situ. PURPOSE: Randomized phase III trial to compare the effectiveness of radiation therapy with that of observation, with or without tamoxifen, in treating women who have ductal carcinoma in situ.

Detailed Description
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OBJECTIVES: Compare the efficacy of whole breast radiotherapy vs observation with or without optional tamoxifen in decreasing or delaying the appearance of local failure (both invasive and in situ) and preventing the need for mastectomy in women with good-risk ductal carcinoma in situ (DCIS) of the breast. Compare distant disease-free survival of patients treated with these regimens. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age (under 50 vs 50 and over), final path margins (negative vs 3-9 mm vs at least 10 mm), mammographic size of primary (no greater than 1 cm vs greater than 1 cm to 2.5 cm), nuclei grade (low vs intermediate), and tamoxifen use (yes vs no). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients undergo observation and may receive optional oral tamoxifen once daily (at the discretion of the physician) for 5 years. Arm II: Beginning within 12 weeks after final surgery, patients receive radiotherapy to the whole breast once daily, 5 days a week, for 3.5-5.5 weeks. Patients may receive optional tamoxifen as in arm I. Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 1,790 patients will be accrued for this study within 6 years.

Official Title
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Phase III Trial of Tamoxifen Alone vs. Tamoxifen Plus Radiation Therapy for Good Risk Duct Carcinoma In-Situ (DCIS) of the Female Breast

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: tamoxifen citrate
* Procedure: adjuvant therapy
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Ductal carcinoma in situ (DCIS) of the breast detected by mammogram at the time of diagnosis Unicentric Lesions ≤ 2.5 cm Low nuclei grade (NG1) or intermediate nuclei grade (NG2) with necrosis in < one third of the involved ducts Inked margins ≥ 3 mm Clinically node negative Non-palpable No suspicious areas on post-operative mammogram taken within 12 weeks after final surgery No bloody nipple discharge No more than 12 weeks since prior final surgery (arm II only) Hormone receptor status: Not specified PATIENT CHARACTERISTICS: Age: 26 and over Sex: Female Menopausal status: Not specified Performance status: Not specified Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Not specified Renal: Not specified Other: Not pregnant or nursing No active connective tissue disorders (e.g., lupus or scleroderma) No prior malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior chemotherapy Endocrine therapy: No other concurrent hormonal therapy (e.g., raloxifene, hormone replacement therapy, or birth control pills) Radiotherapy: No prior radiotherapy Surgery: See Disease Characteristics

Ages Eligible for Study
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Minimum Age: 26 Years
Maximum Age: 120 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: Observation +/- tamoxifen for 5 years<br>Observation +/- tamoxifen 20 mg per day for 5 years | Drug: tamoxifen citrate<br> <br> Procedure: adjuvant therapy<br> <br> |
| Experimental: Radiation therapy +/- tamoxifen for 5 years<br>Radiation therapy to the whole breast +/- tamoxifen 20 mg per day for 5 years | Drug: tamoxifen citrate<br> <br> Procedure: adjuvant therapy<br> <br> Radiation: radiation therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local recurrence (e.g., invasive or noninvasive recurrence) |  | From randomization to date of local failure in the treated breast or last follow-up. Analysis occurs after all patients have been potentially followed for 5 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | From randomization to date of death or last follow-up. Analysis occurs after all patients have been potentially followed for 5 years. | 
| Time to distant metastasis |  | From randomization to date of distant metastasis or last follow-up. Analysis occurs after all patients have been potentially followed for 5 years. | 
| Invasive local recurrence |  | From randomization to date of invasive local failure in the treated breast or last follow-up. Analysis occurs after all patients have been potentially followed for 5 years. | 
| Salvage mastectomy rate |  | Analysis occurs after all patients have been potentially followed for 5 years. | 

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