• Effect of this drug on bone mineral density [ Designated as safety issue: No ]
• Effect of this drug on breast density at 2 years [ Designated as safety issue: No ]
• Effect of this drug on serum hormones, insulin-like growth factor pathway components, and leptin at 3 months and 1 year [ Designated as safety issue: No ]
• Effect of this drug on serum lipids, C-reactive protein, and homocysteine [ Designated as safety issue: No ]
• Effect of this drug on breast tissue trefoil factor 1 and proliferating cell nuclear antigen expression, prolactin, and breast tissue prolactin receptor at 1 year [ Designated as safety issue: No ]

• Effect on bone mineral density
• Effect on breast density at 2 years
• Effect on serum hormones, insulin-like growth factor pathway, components and leptin at 3 months and 1 year
• Effect on serum lipids, C-reactive protein, and homocysteine
• Effect of this drug on breast tissue trefoil factor 1 and proliferating cell nuclear antigen expression, autocrine prolactin, and breast tissue prolactin receptor at 1 year

RATIONALE: High estrogen levels may be associated with dense breast tissue and an increased risk of developing breast cancer. Exemestane may decrease estrogen levels and reduce breast density.

PURPOSE: This phase II trial is studying how well exemestane works in preventing cancer in postmenopausal women who are at high risk of developing invasive breast cancer.

OBJECTIVES:

Primary

• Determine the effect of exemestane on mammographic density at 1 year in postmenopausal women at high risk for invasive breast cancer.

Secondary

• Determine the effect of this drug on bone mineral density in these patients.
• Determine the effect of this drug on breast density at 2 years in these patients.
• Determine the effect of this drug on serum hormones (prolactin, estradiol, progesterone, dehydroepiandrosterone [DHEA], androstenedione, testosterone, and sex hormone-binding globulin), insulin-like growth factor (IGF) pathway components (IGF-I, IGF-II, IGF-binding protein [IGFBP]-2, IGFBP-3, and IGFBP-5), and leptin at 3 months and 1 year in these patients.
• Determine the effect of this drug on serum lipids (total cholesterol, high-density lipoprotein, low-density lipoprotein, apolipoprotein a, apolipoprotein b, triglycerides), C-reactive protein, and homocysteine in these patients.
• Determine the effect of this drug on breast tissue trefoil factor 1 and proliferating cell nuclear antigen expression, prolactin, and breast tissue prolactin receptor at 1 year in these patients.

OUTLINE: This is an open-label study.

Patients receive oral exemestane once daily for 2 years in the absence of the development of invasive breast cancer or unacceptable toxicity.

Quality of life is assessed at baseline and then at 12 and 24 months.

Patients are followed every 6 months.

PROJECTED ACCRUAL: A total of 45 patients will be accrued for this study.

• Breast Cancer
• Precancerous/Nonmalignant Condition

DISEASE CHARACTERISTICS:

• Determined to be at high risk for developing invasive breast cancer by meeting at least 1 of the following criteria:

  • Gail Model risk of ≥ 1.7% for the next 5 years
  • Lobular neoplasia
  • Atypical ductal hyperplasia
  • Ductal carcinoma in situ previously treated with mastectomy or lumpectomy and radiotherapy with or without tamoxifen
  • Deleterious mutations in BRCA1 or 2
  • A prior risk assessment of ≥ 20% chance of carrying BRCA1 or 2 gene mutation
  • History of stage I or II invasive breast cancer that was definitively treated ≥ 2 years ago
• Bone mineral density T-score ≥ -2.5 at anterior-posterior spine by baseline dual energy x-ray absorptiometry scan

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Age

• Postmenopausal

Sex

• Female

Menopausal status

• Postmenopausal, defined as 1 of the following:

  • FSH > 35 U/L
  • No menses for at least 12 months
  • Prior bilateral oophorectomy

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Hemoglobin ≥ 11 g/dL
• No history of clotting or bleeding disorder

Hepatic

• ALT and AST < 2.5 times upper limit of normal (ULN)

Renal

• Creatinine < 1.5 times ULN

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Gastrointestinal

• No active GI disease (e.g., inflammatory bowel disease)

Other

• No history of allergic reactions attributed to compounds of similar chemical or biological composition to exemestane (e.g., anastrozole, letrozole, or formestane)
• No concurrent uncontrolled illness
• No active or ongoing infection
• No psychiatric illness or social situation that would preclude study compliance
• No other cancer except squamous cell or basal cell skin cancer

PRIOR CONCURRENT THERAPY:

Endocrine therapy

• See Disease Characteristics

• More than 3 months since prior and no concurrent hormonal therapy (e.g., oral contraceptives, hormone replacement therapy, tamoxifen, raloxifene, intrauterine device [IUD] with progestins, or corticosteroids)

  • Chronic topical or inhaled steroids allowed
  • Vaginal estrogen allowed
• No prior aromatase inhibitors

Radiotherapy

• See Disease Characteristics

Surgery

• See Disease Characteristics

Other

• More than 2 years since prior anticancer treatment
• At least 30 days since prior investigational agents

• No concurrent use of any of the following drugs:

  • Phenytoin
  • Carbamazepine
  • Rifampin