• Female ≥ 18 years of age pre and post-menopausal

• Metastatic disease (≤ 5 sites of measurable disease by RECIST)

• Eligible for treatment with CDK4/6 + aromatase inhibitors

• Premenopausal status is defined as either:

• Patient had last menstrual period within the last 12 months, OR

• If on tamoxifen or toremifene within the past 14 days, plasma estradiol and FSH must be in the premenopausal range per local normal range, OR

• In case of therapy-induced amenorrhea, plasma estradiol and/or FSH must be in the premenopausal range per local normal range.

• Patients who have undergone bilateral oophorectomy are eligible.

• Post-menopausal status defined as either 1) at least 2 years without menstrual period or 2) patients older than 50 with serological evidence of post-menopausal status or 3) hysterectomized patients of any age with FSH confirmation of post-menopausal status.

• Eastern Cooperative Oncology Group (ECOG) performance status 0-1

• Biopsy proven diagnosis of HR+HER2- metastatic breast cancer. ER expression is \>10%

• Patient needs to be able to understand and demonstrate a willingness to sign a written informed consent document

• Hematological WBC ≥ 2000/uL

• Absolute neutrophil count (ANC) ≥1500/µL

• Platelets ≥100 000/µL

• Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/La Renal Creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 × ULN OR

• ≥30 mL/min for the participant with creatinine levels \>1.5 × institutional ULN Hepatic Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels \>1.5 × ULN

• AST (SGOT) and ALT (SGPT) ≤2.5 × ULN

• Coagulation International normalized ratio (INR) OR prothrombin time (PT)

• Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless the participant is receiving anticoagulant therapy if PT or aPTT is within the therapeutic range of intended use of anticoagulants