Tamoxifen in Preventing Breast Cancer in Women at Increased Risk for Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. The use of tamoxifen may be effective in preventing breast cancer. PURPOSE: This randomized phase II trial is studying tamoxifen to see how well it works compared to placebo in preventing breast cancer in women who are at increased risk for the disease.

Detailed Description
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OBJECTIVES: Compare molecular markers of proliferation and apoptosis in breast epithelial tissue of women at increased risk for breast cancer treated with tamoxifen vs placebo. Compare the modulation of markers of genomic instability in breast epithelial tissue of patients treated with these drugs. Compare serum levels of IGF-1, IGF-2, and IGFBP-3 of these patients at baseline and after treatment with these drugs. OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to estimated 5-year breast cancer risk (1.67-5% vs ≥ 5%), presence of atypical ductal hyperplasia (yes vs no), and menopausal status (premenopausal vs postmenopausal). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive oral tamoxifen once daily. Arm I: Patients receive oral placebo once daily. Treatment in both arms continues for 3 months in the absence of invasive breast cancer or unacceptable toxicity. Patients undergo core needle biopsy and fine needle aspiration biopsy at baseline and then at the completion of study treatment (for premenopausal patients); exactly 84 days after the first biopsy (for postmenopausal patients); or on the first or second day of the menstrual cycle on or after 84 days (during the third menstrual cycle) after the first dose of study medication (for patients with irregular menses). Patients are followed at 30 days. PROJECTED ACCRUAL: A total of 130 patients (65 per arm) will be accrued for this study within 30 months.

Official Title
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An Exploratory Study to Identify Potential Surrogate Endpoint Biomarkers That Are Modulated by Tamoxifen vs. Placebo in Women With an Increased Risk for Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: tamoxifen citrate


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: At increased risk for breast cancer, as defined by 1 of the following criteria: Histologically confirmed lobular carcinoma in situ (LCIS) treated by local excision only Composite increased breast cancer risk of ≥ 1.67% over 5 years, based on the following criteria: Age Number of first-degree female relatives with breast cancer One or more prior breast biopsies Fine-needle aspiration cytology of a non-cystic lesion in lieu of an open biopsy is considered a biopsy Prior diagnosis of atypical hyperplasia of the breast Age at first live birth Nulliparity Race Age at onset of menarche No prior or suspected invasive breast cancer or ductal carcinoma in situ No clinical evidence of malignancy by physical examination, including a breast examination within the past 3 months No evidence of suspicious or malignant disease or uncharacterized lesions on bilateral mammogram within the past 6 months Normal gynecologic examination, including a bimanual pelvic examination and, if indicated, pap smear within the past 12 months Hormone receptor status: Not specified PATIENT CHARACTERISTICS: Age 35 and over Sex Female Menopausal status Premenopausal and ovulating*, defined as having regular menses for the past 6 months OR irregular menses with follicular phase (i.e., day 3) follicle-stimulating hormone level < 20 mIU/mL OR Postmenopausal NOTE: * Ovulation is determined by day 21 progesterone level > 3 ng/mL Performance status ECOG 0-2 Life expectancy Not specified Hematopoietic Complete blood count normal No active bleeding disorder (e.g., qualitative or quantitative platelet abnormality, hemophilia, or von Willebrand's disease) Hepatic Liver function tests normal Renal Not specified Cardiovascular No prior deep-vein thrombosis except a single occurrence related to lower extremity trauma No prior cerebral vascular accident No prior transient ischemic attack Pulmonary No prior pulmonary embolus except a single occurrence related to lower extremity trauma Other No saline or silicone breast implants No known allergy to tamoxifen No macular degeneration No malignancy within the past 5 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix No nonmalignant disease that would preclude administration of tamoxifen No psychiatric condition, including a history of clinical depression or addictive disorder, that would preclude giving informed consent or study compliance Not pregnant or nursing Negative pregnancy test Fertile patients must use effective nonhormonal contraception during and for 3 months after study participation PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy No prior systemic adjuvant chemotherapy for LCIS Endocrine therapy No prior tamoxifen, raloxifene, or other selective estrogen-receptor modulators At least 3 months since prior and no concurrent use of any of the following drugs: Estrogen or progesterone replacement therapy Oral contraceptives Androgens Luteinizing hormone-releasing hormone analogs Prolactin inhibitors Antiandrogens Steroids No concurrent steroids for asthma Radiotherapy No prior radiotherapy for LCIS Surgery No prior bilateral prophylactic mastectomy No prior mastectomy for LCIS Other Concurrent nonhormonal medications allowed No concurrent warfarin or cholestyramine No prior or concurrent participation in any other cancer prevention study Patients treated with placebo on protocol NSABP-P-1 are eligible

Ages Eligible for Study
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Minimum Age: 35 Years
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
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: tamoxifen citrate|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma levels of hormones and binding proteins as measured by ELISA, IHC, and TUNEL at baseline and 3 months |  |  | 
| Markers of proliferation and apoptosis in breast cells as measured by quantitative MSP at baseline and 3 months |  |  | 
| Promoter-region methylation as assessed by microarrays at baseline and 3 months |  |  | 
| Gene expression |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer, lobular breast carcinoma in situ, breast cancer in situ