Letrozole With or Without Zoledronate in Treating Healthy Postmenopausal Women With High Breast Density

OBJECTIVES:

Primary

• Compare the percent change in breast density in healthy postmenopausal women with high breast density treated with placebo only vs letrozole and placebo vs letrozole and zoledronate.
• Compare the percent change in biochemical markers of bone turnover in participants treated with these regimens.

Secondary

• Compare the bone density in participants treated with these regimens.
• Compare growth hormone release and insulin-like growth factor levels in participants treated with these regimens.
• Compare the incidence and severity of adverse events in participants treated with these regimens.

OUTLINE: This is a randomized, placebo-controlled, double-blind, multicenter, pilot study. Participants are stratified according to prior hormone replacement therapy (HRT) use (discontinued HRT > 5 years ago or no prior HRT use vs discontinued HRT 1-5 years ago). Patients are randomized to 1 of 3 treatment arms.

• Arm I: Participants receive oral placebo once daily for 12 months and placebo IV over 15 minutes on day 0 and at 6 months.
• Arm II: Participants receive oral letrozole once daily for 12 months and placebo IV over 15 minutes on day 0 and at 6 months.
• Arm III: Participants receive oral letrozole once daily for 12 months and zoledronate IV over 15 minutes on day 0 and at 6 months.

In all arms, treatment continues in the absence of unacceptable toxicity.

After completion of study treatment, participants are followed at 3 months.

PROJECTED ACCRUAL: A total of 120 participants (40 per treatment arm) will be accrued for this study.

DISEASE CHARACTERISTICS:

• Healthy participant
• Postmenopausal for > 5 years
• Breast density ≥ 50% by digitized mammography
• No history of breast cancer, breast implant, or gynecological malignancy
• No osteoporosis or postmenopausal fractures

• T-scores ≥ -2.0 by dual-energy x-ray absorptiometry (DEXA) scan

PATIENT CHARACTERISTICS:

Age

• 18 and over

Sex

• Female

Menopausal status

• See Disease Characteristics

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• AST or ALT ≤ 3 times normal

Renal

• Creatinine ≤ 1.5 mg/dL

Cardiovascular

• No cardiac disease

Other

• Nonsmoker
• Vitamin D ≥ 15 ng/mL
• No history of chronic medical or psychiatric condition or laboratory abnormality that would preclude study compliance or participation
• No alcohol consumption of > 2 alcoholic drinks per day
• No malabsorption

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• At least 1 year since prior hormone replacement therapy
• No concurrent steroids, parathyroid hormone, or raloxifene

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• No other concurrent medication known to affect calcium and bone metabolism (e.g., anticoagulants, antiseizure medications, bisphosphonates, or calcitonin)