Estrogen in Postmenopausal Women With ER Positive Metastatic Breast Cancer After Failure of Sequential Endocrine Therapy

A Single Arm Phase II Study of Pharmacologic Dose Estrogen in Postmenopausal Women With Hormone Receptor-Positive Metastatic Breast Cancer After Failure of Sequential Endocrine Therapies

This trial seeks to confirm the response rate for estrace treatment in a patients with hormone receptor positive metastatic breast cancer heavily pre-treated with modern endocrine therapies.

Prior to the current standard of care utilizing estrogen deprivation or antiestrogen therapy to treat hormonally sensitive breast cancers, treatment with pharmacologic doses of estrogen was a common technique used to treat post-menopausal women with hormone sensitive metastatic disease that resulted in durable responses with regression of disease. A randomized trial comparing tamoxifen and pharmacologic doses of estrogen demonstrated similar rates of response with long-term follow-up data confirming a survival benefit for those treated with the estrogen preparation. Additional data has shown that post-menopausal women with hormonally sensitive tumors that have progressed on prior endocrine therapies responded to treatment with pharmacologic doses of estrogen. These data, coupled with pre-clinical data that postmenopausal levels of estrogen can be used to cause apoptosis (programmed cell death within the tumor) and tumor regression in exhaustively treated endocrine resistant disease form the rationale for the proposed clinical trial. This trial seeks to confirm the response rate for estrace treatment in a patient population heavily pre-treated with modern endocrine therapies.

Inclusion Criteria:

• Histologically confirmed estrogen and/or progesterone receptor-positive breast cancer metastatic breast cancer
• Clinically determined evaluable disease
• Post-menopausal woman
• Previous clinical benefit from prior anti-estrogen therapies and subsequent failure of at least 2 prior endocrine therapies.
• May have had chemotherapy for adjuvant &/or metastatic disease.
• May have had radiation therapy but not to the only site of disease.
• Ecog performance status </= 2.
• Life expectancy of > 6 months

Exclusion Criteria:

• Chemotherapy or radiotherapy within 1 week of beginning treatment in the clinical trial
• Brain metastasis
• Prior history of or active thrombophlebitis, deep venous thrombosis or pulmonary embolus
• Current vaginal bleeding
• Hypercalcemia or hypocalcemia
• History of or active hepatic adenoma
• No other malignancies within the past 5 years with the exception of curatively treated basal cell or squamous cell carcinoma of the skin or carcinoma in-situ of the cervix