Raloxifene and Goserelin in Preventing Breast Cancer in Women With a Family History of Breast Cancer

OBJECTIVES:

• Compare the feasibility of raloxifene and goserelin versus no medical intervention in women at high genetic risk for developing breast cancer.
• Compare the incidence of adverse effects in patients treated with these regimens.
• Compare the effect of these regimens on bone density, biochemical markers of bone turnover, and lipid profiles in these patients.
• Compare the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center. Patients are randomized to one of two treatment arms.

• Arm I: Patients receive goserelin subcutaneously once every month and oral raloxifene daily for 6-12 months.
• Arm II: Patients are screened for breast cancer every 6 months. In both arms, patients undergo annual mammograms.

Quality of life is assessed at baseline and at 1, 3, 6, and 12 months.

Patients are followed for 5 years.

PROJECTED ACCRUAL: A total of 150 patients (75 per treatment arm) will be accrued for this study.

DISEASE CHARACTERISTICS:

• High genetic risk of developing breast cancer defined as one or more of the following:

• BRCA1 or BRCA2 germ-line mutation
• First-degree relative of known BRCA1 or BRCA2 mutation carrier
• Family with 4 or more relatives diagnosed with female or male breast cancer or ovarian cancer before the age of 60
• Two first-degree relatives diagnosed with breast cancer before the age of 40
• p53 germ-line mutation (classical Li-Fraumeni syndrome (LFS) only)
• First-degree relative of a carrier in a family with classical LFS
• Risk equivalent to any of the above confirmed by clinical geneticist
• No evidence of breast cancer by mammography

• Suspicious lesions must be confirmed as non-malignant
• No prior breast cancer
• No prior prophylactic mastectomy
• No plan for alternative prevention measures within the next 12 months
• Hormone receptor status:

• Not specified

PATIENT CHARACTERISTICS:

Age:

• 30 to 45

Sex:

• Female

Menopausal status:

• Premenopausal (follicle-stimulating hormone in premenopausal range if not menstruating)

Performance status:

• Not specified

Life expectancy:

• More than 10 years (excluding breast cancer risk)

Hematopoietic:

• Not specified

Hepatic:

• Adequate liver function

Renal:

• Adequate renal function

Cardiovascular:

• No prior deep vein thrombosis

Pulmonary:

• No prior pulmonary embolism

Other:

• Not pregnant
• Fertile patients must use effective nonhormonal contraception
• No psychological disorder that would preclude study compliance
• No prior malignancy within the past 5 years except curatively treated nonmelanoma skin cancer or cervical cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• Not specified

Endocrine therapy:

• No concurrent hormonal therapy (e.g., oral contraception or hormone replacement therapy)

Radiotherapy:

• Not specified

Surgery:

• See Disease Characteristics

Other:

• At least 30 days or 5 half-lives since prior investigational drugs
• No concurrent anticoagulants