Anastrozole in Preventing Breast Cancer in Postmenopausal Women at Increased Risk of Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development of cancer. Anastrozole may be effective in preventing breast cancer. PURPOSE: This randomized clinical trial is studying how well anastrozole works in preventing breast cancer in postmenopausal women who are at increased risk for the disease.

Detailed Description
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OBJECTIVES: Primary Determine the effectiveness of anastrozole in preventing breast cancer in postmenopausal women at increased risk for the disease. Secondary Determine the role of this drug in preventing estrogen receptor-positive breast cancer in these participants. Determine the effect of this drug on breast cancer mortality in these participants. Determine the effect of this drug on other cancers, cardiovascular disease, fracture rates, and non-breast cancer deaths in these participants. Determine the tolerability and acceptability of side effects of this drug in these participants. OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Participants are stratified according to participating center. Participants are randomized to 1 of 2 treatment arms. Arm I: Participants receive oral anastrozole daily for 5 years. Arm II: Participants receive an oral placebo daily for 5 years. In both arms, treatment continues in the absence of the development of breast cancer (including ductal carcinoma in situ), a drop in the T-score below minus 4, or the occurrence of a new fragility fracture. Participants are followed for at least a further 5 years. Peer Reviewed and Funded or Endorsed by Cancer Research UK ACCRUAL: A total of 3,864 participants were recruited for this study over 10 years.

Official Title
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International Breast Cancer Intervention Study

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: anastrozole
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Meets at least 1 of the relative risk factors based on age as follows: 45 to 70 years of age: First-degree relative who developed breast cancer at ≤ 50 years of age First-degree relative who developed bilateral breast cancer Two or more first- or second-degree relatives who developed breast cancer or ovarian cancer Participants having both relatives who are second degree and on the opposite sides of the family must have at least one that was diagnosed at ≤ 50 years of age Nulliparous (or first birth at ≥ 30 years of age) and a first-degree relative who developed breast cancer Benign biopsy with proliferative disease and a first-degree relative who developed breast cancer Mammographic opacity covering at least 50% of the breast in the absence of hormone replacement therapy within the past 3 months 60 to 70 years of age: First-degree relative with breast cancer at any age Age at menopause ≥ 55 years Nulliparous or age at first birth ≥ 30 years 40 to 44 years of age: Two or more first- or second-degree relatives who developed breast cancer or ovarian cancer at ≤ 50 years of age First-degree relative with bilateral breast cancer who developed the first breast cancer at ≤ 50 years of age Nulliparous (or first birth at ≥ 30 years of age) and a first-degree relative who developed breast cancer at ≤ 40 years of age Benign biopsy with proliferative disease and a first-degree relative who developed breast cancer at ≤ 40 years of age All age groups (40 to 70 ears of age) with a 10-year risk > 5% who do not fit into the above categories are allowed Clearly apparent family history AND/OR other risk factors indicating appropriate increased risk of breast cancer for age The following prior breast conditions are allowed (for all age groups): Lobular carcinoma in situ Atypical ductal or lobular hyperplasia in a benign lesion Ductal carcinoma in-situ (DCIS), diagnosed within the past 6 months, and treated by mastectomy No evidence of breast cancer on mammogram within the past year Hormone receptor status: For patients with prior DCIS, estrogen- or progesterone-receptor status must have been positive Must have had greater than or equal to 5% positive cells PATIENT CHARACTERISTICS: Age 40 to 70 Sex Female Menopausal status Postmenopausal, defined as at least 1 of the following: Over 60 years of age Bilateral oophorectomy ≤ 60 years of age with a uterus and amenorrhea for at least 12 months ≤ 60 years of age without a uterus and with follicle-stimulating hormone levels > 30 IU/L Performance status Not specified Life expectancy At least 10 years Hematopoietic Not specified Hepatic Not specified Renal Not specified Other Psychologically and physically suitable to receive 5 years of anti-estrogen therapy No cancer within the past 5 years except non-melanoma skin cancer or carcinoma in situ of the cervix No evidence of osteoporosis or fragility fractures within the spine Participants with a T-score > minus 4 and no more than 2 fragility fractures are allowed No concurrent severe disease that would place the participant at unusual risk or confound the results of the study No other medical condition that would preclude the ability to receive the study treatment PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy Not specified Endocrine therapy No prior tamoxifen, raloxifene, or other selective estrogen receptor modulator (SERM) use for more than 6 months in duration unless an IBIS-I participant (must have been off trial therapy for at least 5 years. No concurrent tamoxifen, raloxifene, or other SERM No concurrent estrogen-based hormone replacement therapy No concurrent systemic estrogen replacement therapy, including vaginal estrogen preparations Radiotherapy Not specified Surgery See Disease Characteristics No prior prophylactic mastectomy No concurrent prophylactic mastectomy Other More than 6 months since prior investigational drugs

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: anastrozole<br>anastrozole 1mg | Drug: anastrozole<br>* aromatase inhibitor<br>* Other names: Arimidex;|
| Placebo Comparator: placebo<br>anastrozole 1mg PLACEBO | Drug: placebo<br>* Arimidex placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Development of histologically confirmed breast cancer, both invasive and non-invasive with median follow-up at 5 years |  | Dec 2013 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Breast cancer mortality with median follow-up at 10 years |  | Dec 2018 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer, chemoprevention