Adjuvant Tamoxifen Compared With Anastrozole in Treating Postmenopausal Women With Ductal Carcinoma In Situ

Study Overview
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Brief Summary
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RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using either tamoxifen or anastrozole may fight breast cancer by blocking the use of estrogen. It is not yet known whether tamoxifen is more effective than anastrozole in preventing breast cancer after surgery for ductal carcinoma in situ. PURPOSE: This randomized phase III trial is studying how well adjuvant tamoxifen works compared to anastrozole in treating postmenopausal women who have undergone surgery to remove ductal carcinoma in situ.

Detailed Description
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OBJECTIVES: Primary Compare the efficacy of adjuvant tamoxifen vs anastrozole, in terms of local control and prevention of contralateral disease, in postmenopausal women with locally excised ductal carcinoma in situ. Compare side effect profiles of these drugs in these patients. Secondary Compare the efficacy of these drugs, according to the receptor status of the primary or recurrent cancer in these patients. Compare the rate of breast cancer recurrence and growth of new contralateral tumors after cessation of treatment with these drugs in these patients. Compare breast cancer mortality in patients treated with these drugs. Compare the effect of these drugs on other cancers, cardiovascular disease, fracture rates, and non-breast cancer deaths in these patients. Compare the tolerability and acceptability of side effects experienced by patients treated with these drugs. OUTLINE: This is a randomized, double-blind, multicentre study. Patients are stratified according to participating centre. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive oral tamoxifen and oral placebo once daily. Arm II: Patients receive oral anastrozole and oral placebo once daily. In both arms, treatment continues for 5 years in the absence of disease recurrence or unacceptable toxicity. Patients are followed annually for 5 years and a further 5 years (minimum) off treatment. Peer Reviewed and Funded by Cancer Research UK. Sponsored by Queen Mary University of London ACTUAL ACCRUAL: A total of 2,980 patients were accrued for this study over 9 years.

Official Title
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International Breast Cancer Intervention Study II (IBIS-II) (DCIS)

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: tamoxifen citrate
* Drug: Anastrozole


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of ductal carcinoma in situ within the past 6 months Locally excised with tumor-free margins at least 1 mm Hormone receptor status: Estrogen or progesterone receptor positive Equal to or greater than 5% positive cells PATIENT CHARACTERISTICS: Age 40 to 70 Sex Female Menopausal status Postmenopausal, defined as meeting at least 1 of the following criteria: Over age 60 Prior bilateral oophorectomy Age 60 or under with a uterus AND amenorrhea for at least the past 12 months Age 60 or under without a uterus AND follicle-stimulating hormone greater than 20 IU/L Performance status Not specified Life expectancy At least 10 years Hematopoietic Not specified Hepatic Not specified Renal Not specified Cardiovascular No prior deep vein thrombosis No prior transient ischemic attack No prior cerebrovascular accident Pulmonary No prior pulmonary embolism Other No unexplained postmenopausal bleeding No other cancer within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix No other concurrent medical condition that would preclude study therapy, place the patient at unusual risk, or confound study results No evidence of osteoporosis Fragility fractures within the spine allowed if T-score level is greater than -4 and consist of no more than 2 fractures Psychologically and physically suitable for 5 years of study therapy PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy Not specified Endocrine therapy No prior or concurrent tamoxifen use lasting more than 6 months unless treatment was completed more than 5 years ago. Women in IBIS-I can join if off trial therapy for at least 5 years. No prior or concurrent raloxifene use lasting more than 6 months unless treatment was completed more than 5 years ago. No other prior or concurrent selective estrogen-receptor modulator use lasting more than 6 months unless treatment was completed more than 5 years ago No concurrent systemic estrogen-based hormone replacement therapy, including vaginal estrogen preparations Radiotherapy Not specified Surgery See Disease Characteristics No prior mastectomy No planned prophylactic mastectomy Other At least 3 months since prior unapproved or experimental agents No concurrent anticoagulants

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 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: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Anastrozole<br> | Drug: Anastrozole<br>* Anastrozole 1mg + Tamoxifen placebo<br>* Other names: Arimidex;|
| Active Comparator: Tamoxifen<br> | Drug: tamoxifen citrate<br>* Tamoxifen 20mg + Anastrozole placebo<br>* Other names: Nolvadex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Development of histologically confirmed breast cancer, both invasive and non-invasive with median follow-up at 5 years |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To examine the effect of tamoxifen vs anastrozole on breast cancer mortality |  | 7 years | 

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