BRCA1 Mutation, Breast Cancer
Conditions
Keywords
breast cancer, BRCA1 mutation carrier
Brief summary
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
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.
Interventions
OTHERimmunohistochemistry staining method
OTHERlaboratory biomarker analysis
PROCEDUREneedle biopsy
BIOLOGICALrecombinant human chorionic gonadotropin
GENETICmicroarray analysis
Sponsors
National Cancer Institute (NCI)
Fox Chase Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
20 Years to 40 Years
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | 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 |
Countries
Austria, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Recombinant Human Chorionic Gonadotropin Patients receive recombinant human chorionic gonadotropin subcutaneously three times weekly. Treatment continues weekly for 90 days in the absence of unacceptable toxicity.
recombinant human chorionic gonadotropin
microarray analysis
immunohistochemistry staining method
laboratory biomarker analysis
needle biopsy | 2 |
| Total | 2 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Inconclusive data due to inadequate sample collection | 2 |
Baseline characteristics
| Characteristic | Recombinant Human Chorionic Gonadotropin |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Region of Enrollment Austria | 1 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 2 |
| other Total, other adverse events | 0 / 2 |
| serious Total, serious adverse events | 0 / 2 |
Outcome results
Primary
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
Time frame: 90 days and 270 days from baseline
Population: No results were obtained