OBJECTIVES:

• Evaluate the clinical safety and toxicity of raloxifene in combination with exemestane in postmenopausal women with a history of stage 0 (ductal carcinoma in situ), I, II, or III breast cancer who have no clinical evidence of disease after completion of all planned adjuvant therapy.
• Evaluate the effects of this combination on plasma concentrations of estrogens, markers of bone turnover and bone mineral density, serum lipoprotein profile, and quality of life in this patient population.
• Determine the pharmacokinetics and the pharmacodynamics of this combination in these patients.
• Determine the feasibility of using mammography and breast MRI to assess the effects of this drug combination on radiographic breast density.

OUTLINE: This is a randomized study. Patients are randomized to one of two treatment arms.

• Arm I: Patients receive oral raloxifene once a day for 2 weeks.
• Arm II: Patients receive oral exemestane once a day for 2 weeks. After 2 weeks of single agent therapy, all patients receive combination therapy with oral raloxifene and oral exemestane once a day for 1 year in the absence of unacceptable toxicity or disease recurrence. At the end of 1 year, patients may continue receiving raloxifene alone or raloxifene plus exemestane for a maximum duration of 5 years.

Quality of life is assessed at baseline, and then at 3, 6, and 12 months. Patients who continue treatment after 1 year have quality of life assessed at 24, 36, 48, and 60 months.

Patients are followed every 3 months for the first year. Patients who continue treatment after 1 year are followed every 6 months through the fifth year.

PROJECTED ACCRUAL: A total of 30 patients (15 per arm) will be accrued for this study.

DISEASE CHARACTERISTICS:

• Stage 0 (ductal carcinoma in situ), I, II, or III breast cancer with no clinical evidence of disease after completion of all planned adjuvant therapy

  • No prior antiestrogen therapy as adjuvant therapy
  • Histologically confirmed history of breast cancer
• CEA and CA15-3 normal
• No prior bilateral mastectomy

• Hormone receptor status:

  • Progesterone and estrogen receptor negative OR
  • Progesterone and/or estrogen receptor positive

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Menopausal status:

• Postmenopausal, as defined by 1 of the following:

  • No spontaneous menses for at least 5 years

    • If prior hysterectomy, but have intact ovaries, must have luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels within postmenopausal range
  • Spontaneous menses within the past 5 years, but amenorrheic (e.g., spontaneous or secondary to chemotherapy, radiotherapy, or hysterectomy) for at least 12 months, and LH and FSH levels within postmenopausal range
  • Bilateral oophorectomy

Sex:

• Female

Performance status:

• Karnofsky 80-100%

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 3,000/mm^3

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• AST no greater than 2 times upper limit of normal

Renal:

• Creatinine no greater than 1.5 mg/dL

Cardiovascular:

• No unstable angina
• No New York Heart Association class III or IV heart disease
• No history of venous thrombosis

Pulmonary:

• No history of pulmonary embolism

Other:

• No prior ovarian or endometrial cancer
• No prior or concurrent osteoporosis, as defined by lumbar spine bone mineral density less than 2.5 SD below the mean value for normal premenopausal women

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• At least 4 weeks since prior chemotherapy for breast cancer

Endocrine therapy:

• See Disease Characteristics
• At least 3 months since prior hormonal therapy
• At least 3 months since prior calcitonin
• No adjuvant tamoxifen

Radiotherapy:

• At least 4 weeks since prior radiotherapy for breast cancer

Surgery:

• See Disease Characteristics
• At least 4 weeks since prior surgery for breast cancer
• More than 2 years since prior initial surgery

Other:

• At least 3 months since prior bisphosphonates