High-Dose Esterified Estrogens in Treating Postmenopausal Women With Metastatic Breast Cancer That Has Failed Previous Hormone Therapy

• Time to disease progression [ Designated as safety issue: No ]
• Toxicity [ Designated as safety issue: Yes ]

RATIONALE: High doses of esterified estrogens may stop the growth of breast cancer cells that no longer respond to hormone therapy.

PURPOSE: This phase II trial is studying how well high-dose esterified estrogens work in treating postmenopausal women with metastatic breast cancer that has failed previous hormone therapy.

OBJECTIVES:

Primary

• Determine the clinical response rate in postmenopausal women with estrogen and/or progesterone receptor-positive metastatic breast cancer that has failed prior sequential endocrine therapy treated with high-dose esterified estrogens (Menest^®).

Secondary

• Determine time to disease progression in patients treated with this drug.
• Determine the toxic effects of this drug in these patients.

OUTLINE: Patients receive oral high-dose esterified estrogens (Menest^®) 3 times daily. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed for 2 months.

PROJECTED ACCRUAL: A total of 18-35 patients will be accrued for this study within 2 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed breast cancer

  • Metastatic disease

• Documented disease progression

  • Must have received and subsequently failed (due to disease progression) ≥ 2 prior sequential endocrine therapies for treatment of metastatic breast cancer

    • Disease progression during adjuvant tamoxifen is considered 1 prior therapy
    • The 2 most recent treatments must have been endocrine agents
• At least 1 objective measurable disease parameter

• Brain metastases allowed provided both of the following criteria are met:

  • Brain metastases were previously treated AND are currently stable
  • Brain metastases are not the only site of metastatic disease

• Hormone receptor status

  • Estrogen and/or progesterone receptor-positive tumor

PATIENT CHARACTERISTICS:

Age

• 18 and over

Sex

• Female

Menopausal status

• Postmenopausal, as defined by any of the following:

  • At least 50 years of age with an intact uterus AND amenorrheic for the past 12 months
  • At least 50 years of age without a uterus AND follicle-stimulating hormone (FSH) level within postmenopausal range
  • Under 50 years of age and FSH level within postmenopausal range
  • Prior bilateral oophorectomy

Performance status

• ECOG 0-2

Life expectancy

• At least 6 months

Hematopoietic

• Adequate hematologic function

Hepatic

• Adequate hepatic function
• Bilirubin ≤ 1.5 times upper limit of normal
• No history of hepatic adenoma

Renal

• Adequate renal function
• No history of hypercalcemia or severe hypocalcemia

Cardiovascular

• No history of thrombophlebitis or thromboembolic disorders associated with prior estrogen use
• No active thrombophlebitis or thromboembolic disorders
• No history of uncontrolled hypertension

Other

• Not pregnant
• No undiagnosed abnormal vaginal bleeding
• No other serious medical illness
• No psychiatric illness that would preclude giving informed consent
• No other invasive malignancy within the past 5 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• Prior chemotherapy for metastatic disease allowed
• Prior adjuvant chemotherapy allowed

Endocrine therapy

• See Disease Characteristics

Radiotherapy

• Prior radiotherapy allowed provided the only site of measurable disease was not irradiated

Surgery

• Not specified