Adjuvant Tamoxifen Compared With Anastrozole in Treating Postmenopausal Women With Ductal Carcinoma In Situ (IBIS-II DCIS)

Queen Mary University of London

Status and phase: Completed; Phase 3

Conditions: Breast Cancer

Treatments: Drug: tamoxifen citrate; Drug: Anastrozole

Study type: Interventional

Funder types: Other

Identifiers

NCT00072462

ISRCTN37546358

EU-20226

ISRCTN31488319

BIG-5-02

IBCSG-31-03-DCIS

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 2,980 patients

Sex: Female

Ages: 40 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

    • 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: Quadruple Blind

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2,980 participants in 2 patient groups

Anastrozole

Active Comparator group

Treatment:

Drug: Anastrozole

Tamoxifen

Active Comparator group

Treatment:

Drug: tamoxifen citrate