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

Queen Mary University of London2,980 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Eligibility

Sex: FEMALEMin age: 40 YearsMax age: 70 Years

Medical Language ↔ Plain English

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

Locations (97)

Australia

Newcastle, Australia

Austrian Breast & Colorectal Cancer Study Group

Vienna, Austria

Belgium

Leuven, Belgium

Chile

Santiago, Chile

Institut Sainte Catherine

Avignon, France

Institut Bergonie

Bordeaux, France

Outcomes

Primary Outcomes

Number of Participants With Breast Cancer Recurrence, Including Recurrent DCIS and New Contralateral Tumours

Time frame: Date of the breast cancer occurrence is defined as the date of the confirmation of the specific event (from randomisation to date of occurrence). Data presented is from randomisation to study completion, median follow-up was 11.6 years (IQR: 9.9-13.5).

Secondary Outcomes

Number of Participants With ER+ Breast Cancer Recurrence, Including Recurrent DCIS and New Contralateral Tumours

Number of Participants With ER- Breast Cancer Recurrence

Number of Breast Cancer Deaths

Time frame: Date of the death is defined as the date of the confirmation of the specific event (from randomisation to date of occurrence). Data presented is from randomisation to study completion, median follow-up was 11.6 years (IQR: 9.9-13.5).

Number of Non-breast Cancer Deaths