Raloxifene in Preventing Breast Cancer in Premenopausal Women

OBJECTIVES:

• Determine the safety and tolerability of raloxifene in premenopausal women at high risk of developing invasive breast cancer.
• Determine the effect of raloxifene on blood steroid hormone levels (luteinizing hormone, estradiol, progesterone) and carotenoid levels during the menstrual cycle in these participants.
• Determine the effect of raloxifene on the endometrium and ovaries in these participants.
• Determine the effect of raloxifene on biochemical markers of bone metabolism, lipid profiles, and fibrinogen in these participants.
• Determine the effect of raloxifene on health-related quality of life of these participants.
• Determine the effect of raloxifene on bone mineral density in the spine and hip of these participants.

OUTLINE: This is an open-label study.

Participants are medically evaluated, followed by an observation period of 1 to 2 menstrual cycles. After the observation period, participants receive oral raloxifene once daily for 2 years.

Quality of life is assessed 1 week prior to study drug administration and at 6, 12, 24 and 36 months after study drug administration.

Participants are followed for 1 year.

PROJECTED ACCRUAL: A total of 41 participants will be accrued for this study within 3 years.

DISEASE CHARACTERISTICS:

• At risk for developing invasive breast cancer by virtue of 1 of the following criteria:

• Gail model risk equal to that of an average 60 year old woman as determined using the Gail risk assessment model
• Lobular neoplasia
• Atypical ductal hyperplasia with a positive family history of breast cancer
• Ductal carcinoma in situ previously treated with mastectomy or lumpectomy and radiation
• BRCA1 or BRCA2 mutation-positive genotyping
• Family history consistent with hereditary cancer syndrome of increased breast cancer risk defined as 1 of the following:

• Family with more than 2 breast cancer cases and one or more cases of ovarian cancer diagnosed at any age
• Family with more than 3 breast cancer cases diagnosed before age 50
• Sister pairs with 2 breast cancers, 2 ovarian cancers, or 1 breast and 1 ovarian cancer diagnosed before age 50
• Premenopausal

• Menstrual cycle of 26-35 days
• No change in menstrual pattern within the past 6 months (no irregularities)
• FSH level less than 20 mIU/mL
• Hormone receptor status:

• Not specified

PATIENT CHARACTERISTICS:

Age

• 23 to 47

Sex

• Female

Menopausal status

• Premenopausal

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• No history of bleeding disorder

Hepatic

• No history of cirrhosis of the liver
• SGOT/SGPT no greater than 3 times upper limit of normal (ULN)

Renal

• Creatinine no greater than 1.7 mg/dL

Cardiovascular

• No history of pulmonary embolism or deep venous thrombosis

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile participants must use effective non-hormonal contraception (e.g. barrier methods, spermicides, or surgical methods) during and for 3 months after study
• No history of infertility with a suspected ovarian etiology or recurrent ovarian cysts
• No allergy to raloxifene
• No dysfunctional uterine bleeding
• No menorrhagia
• No cervical dysplasia or significant uterine pathology requiring concurrent surgery
• No medical or psychiatric disorder that would preclude study participation
• Normal CA 125 levels

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• At least 6 months since prior steroid therapy (e.g., tamoxifen, estrogen, DHEA, anabolic steroids, or oral contraceptives)

Radiotherapy

• See Disease Characteristics

Surgery

• See Disease Characteristics
• No prior hysterectomy