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

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.

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.

Eligibility Criteria:
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