RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. Deslorelin combined with low-dose add-back estradiol and testosterone (given to replace hormones suppressed by deslorelin) may be effective in preventing breast cancer in at-risk women.

PURPOSE: This phase II trial is studying how well giving deslorelin together with estradiol and testosterone works in preventing breast cancer in premenopausal women who are at high risk for this disease.

OBJECTIVES:

I. Assess the effects on the breast of treatment with the gonadotropin-releasing hormone agonist (GnRHA)-based regimen in breast cancer (BRCA) gene mutation carriers, including correlation of changes in mammographic and magnetic resonance imaging (MRI) densities with tissue morphometrics and biomarkers.

II. Evaluate perspectives about risk reduction options and impact on quality-of-life (QOL) measures of participation in the chemopreventive protocol and in risk reduction surgery.

OUTLINE:

GROUP 1: Patients receive deslorelin, estradiol, and testosterone intranasally once daily (QD) for 6 months. Patients then undergo planned risk reduction mastectomy.

GROUP 2: Patients receive deslorelin, estradiol, and testosterone intranasally QD for 10 months. Patients then undergo continued surveillance through 10 months.

After completion of study treatment, patients are followed up every 6 months for 2 years.

Inclusion Criteria:

• Patients must generally be in good health with lab values and physical examination within normal limits
• Known high risk of breast cancer due to BRCA mutation or empiric risk > 30% lifetime by the Claus model
• No evidence or history of pervious cancer, except non-melanoma skin cancer
• Premenopausal women planning risk reduction mastectomy in 6 months or more (Group 1) or continued surveillance (Group 2)
• Prior tubal ligation or willing to use a non-hormonal barrier method of contraception
• Signed the Informed Consent Form document for this study in accordance with all Federal, State and Institutional regulations
• Must be current non-smoker

Exclusion Criteria:

• GnRHA treatment within 12 months of study entry
• Nasal polyposis, atrophic rhinitis, severe allergic or vasomotor rhinitis, or sinusitis requiring current treatment or treatment for more than 3 months in the previous year
• Concurrent medications including: corticosteroids (prednisone, prednisolone, cortisone acetate, Decadron, Deltasone, hydrocortisone, Hydrocortone, Medrol), estrogens, progestins or androgens, including oral, implanted, or injected contraceptive; (At least 6 months must have elapsed since the last use of an implanted or injected contraceptive such as Norplant)
• Pregnant or breast-feeding or have been so in the last six months
• Immeasurable breast density on mammogram