Inclusion Criteria:

- Postmenopausal women with advanced hormone receptor positive (ER and or PgR) breast
cancer, has received prior treatment with an aromatase inhibitor in the advanced
disease setting, and experienced at least 24 weeks of progression free survival. As
long as the patient experienced an aromatase inhibitor response as defined this way,
she is still eligible even if she has received further lines of endocrine therapy,
which may include other aromatase inhibitors or tamoxifen, even if these subsequent
lines of treatment were unsuccessful (see below for permitted chemotherapy and
trastuzumab therapy).

OR

- Postmenopausal women with systemic or unresectable local relapse after taking at
least two years of adjuvant aromatase inhibitor therapy.

- Clinical diagnosis of postmenopausal status is defined as either:

1. Age greater than 50 years and amenorrhea for 1 year

2. Bilateral Surgical ovariectomy

3. Serum FSH and estradiol level in the postmenopausal range before the initiation
of AI therapy.

4. If the patient was receiving an LHRH agonist to maintain a postmenopausal state
during AI therapy this should be continued since recovery of menses would lead
to uncontrolled estrogen exposure and pregnancy during estrogen therapy is
contraindicated.

- Tumor cell expression of ER and/or PgR can be ascertained on either the primary or
the metastatic site. However when both types of tissue are available, the metastatic
site should be used to determine eligibility. ER and/or PgR positive are defined as
at least 10% of malignant cells with positive nuclear staining.

- The patients may have received adjuvant and/or neoadjuvant chemotherapy.

- Prior radiotherapy is permitted as long as it was planned before the start of the
study medication and is completed within 3 weeks of trial medication starting.

- Prior tamoxifen therapy is also permitted as adjuvant or advanced disease therapy.

- Patients with ER+ HER2+ disease are eligible even of they have received trastuzumab
in the past (and even if it was administered in combination with endocrine treatment)
as long as they meet all other eligibility criteria. Trastuzumab therapy must be
held during estradiol treatment.

- Use of prior experimental agents alone or in combination with endocrine therapy is
also permissible, but a wash out of one month is required if the immediate prior
therapy involved a study medication that had not been subject to regulatory approval.

- Prior adjuvant chemotherapy is permitted as well as one line of chemotherapy for
advanced disease.

- Patient must have at least one measurable lesion defined by RECIST criteria. To be
considered measurable, a baseline lesion must have a minimum diameter to compensate
for measurement error: 1 cm for soft tissue lesions, 1 cm for lung lesions including
pleural lesions measured by CT scan, 1 cm for liver lesions measured by CT scan.

- Patients with bone only disease can also be enrolled if they meet the following
criteria:

1. Four or more lesions more than one cm, measurable on CT scan bone windows.

2. At least one tumor marker that is elevated to at least two times the upper limit
of normal.

3. All patients should have a baseline bone scan with X-ray evaluation of all hot
spots, CT chest abdomen and pelvis (with bone windows), and tumor marker
assessment. Also CT scan of the extremities should be done on suspicious areas
seen on X-ray evaluation of all hot spots if these extremity lesions are to be
followed for response.

- The patient must have an ECOG performance status of 0-2

- The patient should have a life expectancy of > 6 months.

- The patient must have adequate hematologic function, defined as ANC >1000/mm3 and
platelets > 75,000/mm3.

- The patient must have adequate renal function, defined as serum creatinine less than
or equal to 1.5 times the upper limit of normal.

- The patient must have adequate liver function defined as serum bilirubin less than or
equal to 1.5 times the upper limit of normal (three times the upper limit of normal
for patients with hereditary benign hyperbilirubinaemia), transaminases (ALT, AST)
less than or equal to 2.5 times the upper limit of normal in patients without liver
metastasis or less than or equal to 5 times the upper limit of normal in patients
with liver metastasis.

- For patients with bone metastasis, treatment with i.v. bisphosphonates during the
trial is mandatory because of the risk of hypercalcemia. Bisphosphonate therapy must
be started before the patient begins protocol therapy.

- Preexisting hypercalcemia should be treated and calcium normalized prior to study
entry.

- The patient must give written informed consent prior to initiation of any invasive
study-related procedures that would otherwise not be performed, and must be able to
comply with scheduled visits and evaluations.

- Inclusion of Women and Minorities: Entry to this study is open to women of all racial
and ethnic subgroups.

- Patients with fasting blood glucose level ≤ 200 mg/dL. If greater, hyperglycemia
must be treated before initiation of study investigations.

Exclusion Criteria:

- Patients with CNS involvement with metastatic breast cancer or life threatening
lymphangitic or large volume lung or liver disease that threatens organ function.

- Patients with history of deep venous thrombosis, pulmonary embolism, stroke, acute
myocardial infarction, congestive cardiac failure, untreated hypertension.

- Ischemic changes on a baseline EKG or other evidence of ischemic heart disease.

- Undiagnosed abnormal genital bleeding

- Untreated cholelithiasis

- Fasting serum triglycerides greater than 400. Patients should be treated and
triglycerides controlled prior to study entry.

- Treatment with fulvestrant within 12 months of study initiation (fulvestrant has been
shown to antagonize estradiol induced apoptosis in preclinical models (5).

- The patient's only qualifying lesion (s) have been previously irradiated or are
scheduled for irradiation following study entry.

- Severe or uncontrolled concomitant disease from other causes.

- EGOG Performance status 3 or 4.

- The patient has previous malignancies other than breast cancer except a) adequately
treated in situ carcinoma of the cervix, b) localized basal or squamous cell
carcinoma of the skin c) any previous malignancy treated with curative intent with a
recurrence risk of less than 30%.

- The patient is unable to understand the informed consent or is unlikely to be
compliant with the protocol.

- More than one line of palliative chemotherapy for advanced disease.