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

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.

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