Recombinant Human Chorionic Gonadotropin in Preventing Breast Cancer in Premenopausal Women With BRCA1 Mutations

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. The use of recombinant human chorionic gonadotropin may prevent breast cancer in premenopausal women with BRCA1 mutations. PURPOSE: This clinical trial is studying recombinant human chorionic gonadotropin in preventing breast cancer in premenopausal women with BRCA1 mutations.

Detailed Description
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OBJECTIVES: Primary Determine whether the genomic profiles of breast epithelial cells of high-breast cancer-risk women, as defined by their positive BRCA1 status and nulliparous condition, express a signature indicative of high-risk. Secondary Determine whether women identified to express a high-breast cancer-risk signature will revert it to a low-risk signature after a 90-day treatment with r-hCG, which should have induced breast differentiation and genomic changes that would serve as biomarkers indicative of decreased breast cancer risk. OUTLINE: Patients receive recombinant human chorionic gonadotropin subcutaneously three times weekly. Treatment continues weekly for 90 days in the absence of unacceptable toxicity. Benign breast tissue specimens are collected by core needle biopsy at baseline, day 90, and day 270. Tissue samples are analyzed by cytopathology for epithelial normality, Ki67 immunohistochemical staining for cell proliferation, cDNA microarray for gene expression, and serum studies for hormone levels and biomarker determinations. After completion of study treatment, patients are followed for 24 weeks.

Official Title
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Genomic Markers of Breast Cancer Prevention Induced by HCG in Women at High Risk

Conditions
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BRCA1 Mutation, Breast Cancer

Intervention / Treatment
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* Biological: recombinant human chorionic gonadotropin
* Genetic: microarray analysis
* Other: immunohistochemistry staining method
* Other: laboratory biomarker analysis
* Procedure: needle biopsy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Asymptomatic women who have a deleterious mutation on the BRCA1 gene Normal, no complaints, no evidence of disease Nulliparous, never pregnant (G0P0) No previous diagnosis of breast or ovarian cancer No known brain metastases Hormone receptor status not specified PATIENT CHARACTERISTICS: ECOG performance status (PS) 0-1 OR Karnofsky PS 90-100% Premenopausal with normal menstrual cycles and intact ovaries Normal ovarian size report from pelvic ultrasound Not pregnant or nursing Negative pregnancy test Fertile patients must use effective barrier contraception No history of allergic reactions attributed to compounds of similar chemical or biologic composition to human chorionic gonadotropin preparations or one of its excipients No uncontrolled intercurrent illness including any of the following: Ovarian enlargement of undetermined origin Ovarian cysts > 2 cm Microcystic ovaries, which might predispose to the development of ovarian hyperstimulation syndrome History of prior cancer other than non-melanoma skin cancer Ongoing or active infection Symptomatic congestive heart failure Unstable angina pectoris Cardiac arrhythmia Severe cognitive deficit or psychiatric illness/social situations that would make her unable to give informed consent or would limit compliance with study requirements PRIOR CONCURRENT THERAPY: At least 6 weeks since prior and no concurrent oral contraceptives or hormone-replacement therapy No concurrent tamoxifen for chemoprevention No concurrent participation in another chemopreventive trial for breast cancer No concurrent medication that could interfere with this study including any of the following: Hormonal contraceptives Androgens Prednisone Thyroid hormones Insulin No other concurrent investigational agents No recent treatment with follicle-stimulating hormone for assisted reproduction No HIV-positive patients on concurrent combination antiretroviral therapy

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 40 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Recombinant human chorionic gonadotropin<br>Patients receive recombinant human chorionic gonadotropin subcutaneously three times weekly. Treatment continues weekly for 90 days in the absence of unacceptable toxicity. | Biological: recombinant human chorionic gonadotropin<br> <br> Genetic: microarray analysis<br> <br> Other: immunohistochemistry staining method<br> <br> Other: laboratory biomarker analysis<br> <br> Procedure: needle biopsy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of Gene Expression in Breast Epithelial Cells Obtained for Asymptomatic High Breast Cancer Risk Nulliparous Premenopausal Women at Baseline, After Treatment With r-hCG at 90 Days, and at 270 Days From Baseline |  | 90 days and 270 days from baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer, BRCA1 mutation carrier