RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using either tamoxifen or anastrozole may fight breast cancer by blocking the uptake 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: Randomized phase III trial to compare the effectiveness of adjuvant tamoxifen with that of anastrozole in treating postmenopausal women who have undergone surgery to remove ductal carcinoma in situ.

Condition	Treatment or Intervention	Phase
intraductal breast carcinoma breast cancer in situ	Drug: anastrozole  Drug: tamoxifen  Procedure: adjuvant therapy  Procedure: antiestrogen therapy  Procedure: aromatase inhibition  Procedure: endocrine therapy  Procedure: hormone therapy	Phase III

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, multicenter study. Patients are stratified according to participating center. 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.

PROJECTED ACCRUAL: A total of 4,000 patients will be accrued for this study within 4 years.

Ages Eligible for Study:  40 Years   -   70 Years,  Genders Eligible for Study:  Both

Criteria

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
• 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 3 months
• No prior or concurrent raloxifene use lasting more than 3 months
• No other prior or concurrent selective estrogen-receptor modulator use lasting more than 3 months
• 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

• No prior participation in the International Breast Cancer Intervention Study
• At least 3 months since prior unapproved or experimental agents
• No concurrent anticoagulants

United Kingdom, England
      Broomfield Hospital, Chelmsford, Essex,  England,  CM1 5ET,  United Kingdom; Recruiting
      Cancer Research UK, London,  England,  WC2A 3PX,  United Kingdom; Recruiting
      Christie Hospital N.H.S. Trust, Manchester,  England,  M20 4BX,  United Kingdom; Recruiting
      City Hospital - Birmingham, Birmingham,  England,  B18 7QH,  United Kingdom; Recruiting
      Colchester General Hospital, Colchester,  England,  United Kingdom; Recruiting
      Frenchay Hospital, Bristol,  England,  BS16 1LE,  United Kingdom; Recruiting
      Guy's and St. Thomas' Hospitals NHS Trust, London,  England,  SE1 9RT,  United Kingdom; Recruiting
      Newcastle Upon Tyne Hospitals NHS Trust, Newcastle upon Tyne,  England,  NE1 4LP,  United Kingdom; Recruiting
      Nottingham City Hospital NHS Trust, Nottingham,  England,  NG5 1PB,  United Kingdom; Recruiting
      Royal Liverpool University Hospital, Liverpool,  England,  L69 3GA,  United Kingdom; Recruiting
      Royal South Hants Hospital, Southampton,  England,  SO14 0YG,  United Kingdom; Recruiting
      St. James's University Hospital at Leeds Teaching Hospital NHS Trust, Leeds,  England,  LS9 7TF,  United Kingdom; Recruiting
      Whittington Hospital, London,  England,  N19 5NF,  United Kingdom; Recruiting
United Kingdom, Northern Ireland
      Belfast City Hospital Trust, Belfast,  Northern Ireland,  BT9 7AB,  United Kingdom; Recruiting
United Kingdom, Scotland
      Ninewells Hospital and Medical School, Dundee,  Scotland,  DD1 9SY,  United Kingdom; Recruiting
      Royal Infirmary of Edinburgh at Little France, Edinburgh,  Scotland,  EH3 9YW,  United Kingdom; Recruiting
      Western Infirmary, Glasgow,  Scotland,  G11 6NT,  United Kingdom; Recruiting
United Kingdom, Wales
      University of Wales College of Medicine, Cardiff,  Wales,  CF14 4XN,  United Kingdom; Recruiting

Study chairs or principal investigators

Jack Cuzick, PhD,  Cancer Research UK   

Study ID Numbers:  CDR0000339738; CRUK-IBIS-II-DCIS; EU-20226; BIG-5-02
Record last reviewed:  January 2004
Record first received:  November 4, 2003
ClinicalTrials.gov Identifier:  NCT00072462
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-11-05