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

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.

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