Treatment of Metastatic Breast Cancer With Fulvestrant Plus Palbociclib or Tamoxifen Plus Palbociclib

For inclusion in the study subjects should fulfill the following criteria: 1. Signed informed consent 2. Patients must have histologically or cytologically confirmed invasive breast cancer that is ER+ (\>1% staining) with radiographical or clinical evidence of metastatic disease a. Measurable and/or non-measurable disease 3. Prior therapies: 1. Patients must have previously received an aromatase inhibitor in the adjuvant, neo-adjuvant or metastatic setting. 2. Patients must have previously received palbociclib in the adjuvant, neo- adjuvant or metastatic setting. If patient is currently taking palbociclib at time of screening for the trial they may continue taking palbociclib. 3. The minimum duration of AI in the adjuvant setting is 2 years. 4. There is no minimum duration of AI in the metastatic setting or neoadjuvant setting. 5. Patients may have been previously treated with an mTOR inhibitor or other investigational agent in addition to an aromatase inhibitor. 6. Prior treatment with tamoxifen is allowed in the adjuvant setting provided that it was followed by a minimum of 2 years of an AI. 4. Brain metastasis is allowed if previously treated, stable and off steroids for a minimum of 56 days 5. Age \> 18 years 6. Male or female breast cancer is allowed 7. Patients may be pre- or post-menopausal; pre-menopausal patients must be on ovarian suppression and must be adequately suppressed on LHRH agonists with estradiol levels in the post-menopausal range a. Premenopausal patients cannot be pregnant and must agree to adequate birth control in addition to ovarian suppression. Agreement by the patient and/or partner to use highly effective, nonhormonal form of contraception or two effective forms of non-hormonal contraception. Contraception use should continue during the duration of study treatment and for at least 6 months after the last dose of study treatment. 8. ECOG performance status 0-2 9. Adequate bone marrow function as indicated by the following, within 14 days of enrollment: 1. ANC ≥ 1500 cells/mm3 2. Platelets ≥ 100,000 cells/ mm3 3. Hemoglobin ≥ 9 g/dL 10. Adequate liver function, as indicated by the following, within 14 days of enrollment. 1. Total bilirubin 1.5 upper limit of normal (ULN) 2. AST 1.5 ULN 3. ALT ≤ 2.5 ULN 4. Alkaline phosphatase ≤ 2.5 ULN with the following exception; ALP ≤ 5× ULN in patients with bone metastases. 11. Adequate hemostatic function as determined by PT, INR and aPTT \< 1.5× ULN (unless on therapeutic coagulation, in which case the adequate level of anticoagulation will be determined by the investigator). 12. Adequate renal function, as indicated by creatinine ≤ 1.5 ULN. Subjects should not enter the study if any of the following exclusion criteria are fulfilled 1. Prior therapy exclusions: 1. Prior therapy with fulvestrant 2. Prior therapy with tamoxifen in the metastatic setting 3. More than 3 prior lines of endocrine therapy in the metastatic setting 4. More than one prior line of chemotherapy in the metastatic setting 2. Washout of 2 weeks is required for aromatase inhibitors; washout of 4 weeks is required for, everolimus or other biological agents with the exception of Palbociclib. 3. Patients must not be receiving any other investigational agent. 4. Patients with symptomatic, untreated CNS metastases are not eligible. 5. Patients may not have significant concurrent illness, infection, pregnancy or lactation 6. Patients must not have a different active malignancy, except for skin basal cell carcinoma, skin squamous cell carcinoma and cervical intraepithelial neoplasia.