• Men or women age ≥ 18 years.

• Patients with a diagnosis of ER+, human epidermal growth factor receptor 2 negative (HER2-) metastatic (Stage IV) breast cancer. Positivity status is defined as \>10% staining for ER and immunohistochemistry (IHC) 0+ or IHC 1 or 2+ staining for HER-2, and fluorescence in situ hybridization (FISH) negative with standard pathology staining methods.

• Patients with de novo metastatic disease at the Screening Visit must undergo a SOC diagnostic biopsy.

• Archived tumor tissue available.

• Women and men with proven locally advanced, locoregionally recurrent or metastatic disease adenocarcinoma of the breast not amenable to curative therapy. Note: patients relapsing while on adjuvant tamoxifen or AI are eligible for this study.

• No prior systemic anticancer therapy for metastatic or advanced disease (chemotherapy targeted therapy or endocrine therapy (ET)).

• Note 1: prior endocrine therapy in the metastatic setting is not allowed unless initiated \<30 days from study initiation or Cycle 1, Day 1 (C1D1).

• Note 2: prior initiation of luteinizing hormone-releasing hormone (LHRH) agonist or bone-directed agents, however, is allowed.

• No visceral crisis. Visceral crisis is defined as advanced, symptomatic, visceral spread that is at risk of life-threatening complication in the short term and that requires chemotherapy.

• Adequate organ and marrow function as defined below:

‣ Hematological

• Absolute neutrophil count (ANC) ≥1,500 cells/mm³

∙ Platelets ≥100,000 cells/mm³

∙ Hemoglobin ≥9.0 g/dL or ≥8.0 g/dL for patients with bone metastases and/or menstruating females with evidence of iron deficiency

⁃ Renal

• Serum creatinine or Measured or calculated creatinine clearance (glomerular filtration rate (GFR) can also be used in place of creatinine or creatinine clearance (CrCl)) ≤ 1.5 x upper limit of normal (ULN) or CrCl ≥ 40 mL/min. CrCl should be calculated per institutional standard.

⁃ Hepatic

• Serum total bilirubin \< 1.0 ULN

∙ Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase (SGOT)) and alanine transaminase (ALT) (serum glutamic-pyruvic transaminase (SGPT)). Aminotransferase (AST and ALT) ≤ 2.5 x ULN or 5 X ULN for patients with liver metastases

∙ Albumin ≥ 2.5 mg/dL

• Measurable disease as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST V.1.1) or non-measurable disease that is evaluable.

⁃ Patients with an Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1.

⁃ Ability to understand and the willingness to sign a written informed consent document.

⁃ Life expectancy \>3 months.

⁃ Postmenopausal women, women with suppressed ovarian function, or premenopausal women, provided they are being treated with monthly LHRH analogues and are willing to continue to receive LHRH agonist therapy for the duration of the trial. Menopausal patients or patients with suppressed ovarian function are defined as follows:

∙ Women with bilateral oophorectomy

‣ Postmenopausal women, as defined by any of the following criteria:

⁃ Age 60 or over

• Age 50-59 years and meets the following criterion:

• Amenorrhea for ≥12 months and follicle-stimulating hormone and estradiol levels within the postmenopausal range

• Women with hysterectomy or chemotherapy-induced amenorrhea. Note: Patients with hysterectomy or chemotherapy-induced amenorrhea must display follicle stimulating hormone and estradiol levels within the postmenopausal range.

⁃ Resolution of all acute toxic effects from prior anticancer therapy or surgical procedures as defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) V 5.0 to grade 1 (except alopecia or other toxicities not considered a safety risk for the patient at Investigator's discretion)