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