Test - Retest Reproducibility of 18F Fluoroestradiol (FES) PET

The experimental FES-PET/CT is required to be completed 0 to 30 days prior to initiation of first-line endocrine therapy for metastatic ER+ breast cancer. Labs and correlative radiology, as directed per clinical care, are required within 60 days prior to FES-PET/CT; and FDG-PET/CT is required within 60 days before the FES-PET/CT. Follow-up will comprise 24 months of standard practice treatment and follow up. Visit 1: Patients will have at least one visit with investigator (or investigator designee) prior to the study to review clinical history and prior treatment of primary breast cancer, and to explain the study. Correlative radiology studies including CT, MRI, or bone scan as per institutional routine clinical care, and any clinically-directed laboratory tests performed as part of metastatic staging must be performed within 60 days of the FES-PET/CT. Visit 2: The patient will have a clinically-directed FDG-PET/CT as part of metastatic staging. The FDG-PET/CT will usually be obtained within 60 days prior to the FES-PET/CT. It may be done up to 30 days before the FES-PET/CT if there has been no endocrine therapy for metastatic disease started before the FES-PET/CT. The FDG-PET/CT and FES-PET/CT cannot be performed on the same day due to the half-life of F-18. The FDG-PET/CT may be done as a research scan, if the patient is unable to obtain a clinically-directed FDG-PET/CT as part of their clinical care or within 60 days of FES PET/CT. The research FDG-PET/CT, in this instance, will be identical in procedure to the institution's clinical FDG-PET/CT. The blood glucose level will be \< 200 mg/dl, before FDG injection, which is institutional standard clinical protocol. The following additional patient data will be obtained: histological diagnosis of primary and/or metastatic disease, date of diagnosis of primary and metastatic disease, gender, height, weight (for BMI), ECOG score, and prior adjuvant and metastatic treatment regimens used. Visit 3 - Day of FES PET/CT: The patient will have an intravenous line placed typically in the hand or arm opposite to the known primary breast cancer, FES will be given by 2 minute infusion, and the dose administered will be approximately 6mCi +/- 20%. After approximately 60+/- 10 minutes of uptake time, the patient will be positioned supine in the PET/CT scanner for standard whole body PET/CT scan from the skull base to mid-thigh. This scan will take approximately 20-30 min. If there are any breast lesions, a higher resolution PEM study of the breast/s may be obtained which make take approximately an additional 30-60 min. A blood sample to be obtained, just before the FES injection, and submitted for hormonal analysis (estradiol and sex hormone binding globulin). Visit 4-Day of Reproducibility FES-PET/CT: The test re-test FES-PET/CT will need to be performed at least 24 hours after the first FES-PET/CT and no later than 10 days following the initial FES study, and it can be done at any time after the FDG-PET/CT. The second FES-PET/CT study must be performed on the same scanner as the first FES-PET/CT and the imaging protocol described in Visit 3 should be closely followed. If there are any breast lesions, a higher resolution PEM study may be obtained which make take approximately an additional 30 min. Visit 5-Week 1 to 4 after first FES-PET/CT: Patients will start endocrine therapy in the period from 0 to 30 days post FES-PET/CT, as per clinical standard.