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

Study Overview
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Brief Summary
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RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming, growing, or coming back. Estrogen can cause the growth of breast cancer cells. Hormone therapy using letrozole may prevent breast cancer by lowering the amount of estrogen the body makes. Zoledronate may prevent bone loss caused by letrozole. Giving letrozole together with zoledronate may prevent breast cancer and reduce bone loss. PURPOSE: This randomized clinical trial is studying letrozole and zoledronate to see how well they work compared to letrozole and placebo or placebo alone in treating healthy postmenopausal women with high breast density.

Detailed Description
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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.

Official Title
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Evaluating the Effect of Letrozole With or Without Concomitant Zoledronic Acid on Estrogen Responsive Targets in Postmenopausal Women

Conditions
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Breast Cancer, Osteoporosis

Intervention / Treatment
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* Drug: letrozole
* Drug: zoledronic acid


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 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
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: letrozole|nan|
|Drug: zoledronic acid|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

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