Letrozole in Preventing Breast Cancer in Postmenopausal Women Who Are at Increased Risk for Breast Cancer Due to 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. The use of letrozole may stop cancer from forming or coming back in postmenopausal women who are at increased risk for breast cancer due to high breast density. PURPOSE: This randomized phase II trial is studying how well letrozole works in preventing breast cancer in postmenopausal women who are at increased risk for breast cancer due to high breast density.

Detailed Description
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OBJECTIVES: Primary Determine the proportion of postmenopausal women who are at increased risk for the development or recurrence of breast cancer, based on high breast density (≥ grade 4), who achieve a decrease in breast density of ≥ 1 grade after treatment with letrozole for 1 year. Secondary Determine whether a decrease in breast density grade is sustained at 1 year in patients treated with this drug. Correlate plasma estrogen profile (E1, E1S, E2) with breast density grade at baseline in these patients. Determine the percentage of patients with breast tissue hyperplasia and atypical hyperplasia, as assessed by histopathological examination of breast tissue biopsies, before and after treatment with this drug. Determine the changes in estrogen profile from baseline, at 1 year, and 1 year after cessation of this drug in these patients. Compare changes in predetermined specific parameters of safety at the end of 1 year of treatment with this drug with baseline evaluations of these patients. Determine whether modifications of these predetermined specific parameters of safety are sustained 1 year after cessation of treatment with this drug in these patients. Determine the general safety of 1 year of treatment with this drug in these patients. Compare the effects of this drug on menopause-specific quality of life of these patients. OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to breast density grade (4/6 vs 5/6 vs 6/6). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive oral letrozole once daily for 1 year in the absence of unacceptable toxicity. Arm II: Patients receive oral placebo once daily for 1 year in the absence of unacceptable toxicity. Menopause-specific quality of life is assessed at baseline and then at 12 and 24 months. After completion of study treatment, patients are followed at 6 months and 1 year. PROJECTED ACCRUAL: A total of 120 patients (80 in arm I and 40 in arm II) will be accrued for this study within 12 months.

Official Title
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A Randomized Feasibility Study of Letrozole in Postmenopausal Women at Increased Risk for Development of Breast Cancer as Evidenced by High Breast Density

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: letrozole
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: At increased risk for the development or recurrence of breast cancer, as defined by 1 of the following: Baseline mammogram indicating mammographic density occupying ≥ 25% (grade 4/6, 5/6, or 6/6) of the breast tissue No suspicion of breast cancer, unless subsequently ruled out Prior ductal carcinoma in situ (DCIS) Untreated disease OR > 6 months since completion of adjuvant endocrine therapy Receptor status of lesion is not required Prior invasive breast cancer Breast cancer must have been surgically removed at time of original diagnosis with no evidence of metastases No clinical evidence of breast cancer Acceptable quality dual-energy x-ray absorptiometry (DEXA) of the L2-L4 postero-anterior (PA) spine and hip performed within past 6 months Bone mass density T-score of either PA spine or hip must be ≥ 2.0 SD below the mean peak bone mass in young normal woman Stable chronic leukemia allowed Hormone receptor status: Hormone receptor-negative, -positive, or -equivocal tumor PATIENT CHARACTERISTICS: Age Postmenopausal Sex Female Menopausal status Postmenopausal, as defined by 1 of the following: Over 55 years of age with spontaneous cessation of menses for ≥ 1 year 55 years of age and under with spontaneous cessation of menses for ≤ 1 year, but amenorrheic (e.g., spontaneous or secondary to hysterectomy) AND follicle-stimulating hormone level > 34.4 IU/L Bilateral oophorectomy Performance status Not specified Life expectancy Not specified Hematopoietic Not specified Hepatic Not specified Renal Not specified Cardiovascular No recent unstable myocardial infarction No prior stroke No high blood pressure No other uncontrolled cardiovascular disease Other Other prior malignancies without metastatic disease allowed Willing and able to complete quality of life questionnaires in either English or French No uncontrolled metabolic or endocrine disease No malabsorption syndrome PRIOR CONCURRENT THERAPY: Biologic therapy No concurrent immunotherapy Chemotherapy No concurrent chemotherapy Endocrine therapy See Disease Characteristics At least 3 months since prior and no concurrent hormone replacement therapy or raloxifene At least 6 months since prior tamoxifen No concurrent steroid therapy No concurrent selective estrogen-receptor modulators No other concurrent endocrine or hormonal therapy Radiotherapy Not specified Surgery See Disease Characteristics

Ages Eligible for Study
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Maximum Age: 120 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Letrozole<br> | Drug: letrozole<br>* 2.5 mg PO daily for 1 year<br>|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* 2.5 mg PO daily for one 1 year<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage change of the BMD parameters from baseline BMD values |  | 7 years | 
| Percentage change of bone biomarker measurements (serum bone alkaline phosphatase and urine N-telopeptide) from baseline values |  | 7 years | 

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