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

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
- 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