Deslorelin Combined With Low-Dose Add-Back Estradiol and Testosterone in Preventing Breast Cancer in Premenopausal Women Who Are at High Risk for This Disease

Phase 2Active Not RecruitingNCT00080756

City of Hope Medical Center11 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Enrollment

Conditions

brca1 Mutation Carrier

Interventions

therapeutic estradiolBIOLOGICAL

0.35mg/100ul per day as a nasal spray

deslorelinDRUG

1mg/100ul per day as a nasal spray

therapeutic testosteroneDRUG

0.275mg/100ul per day as a nasal spray

therapeutic conventional surgeryPROCEDURE

Undergo risk reduction mastectomy

active surveillanceOTHER

Undergo continued surveillance

quality-of-life assessmentPROCEDURE

Ancillary studies

laboratory biomarker analysisOTHER

Correlative studies

Eligibility

Sex: FEMALEMin age: 21 YearsMax age: 48 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Treatment effects and correlation of changes in morphometrics and biomarkers as assessed by mammogram and magnetic resonance image (MRI) densities on days 1 and 300

Time frame: Day 300

Perspectives about risk reduction options and their impact on quality of life (QOL) as assessed by Medical Outcomes 36-item short-form version, Health Perceptions scale, and Body Image scale on days 1, 169, and 300, and then every 6 months for 2 years

Time frame: 2 years