Inclusion Criteria:
* Participants must have histologically or cytologically confirmed diagnosis of hormone positive HER2 negative metastatic breast cancer per ASCO/CAP criteria, with diagnosis established through either a breast/axillary biopsy or biopsy of a metastatic lesion.
1. Estrogen Receptor (ER) or Progesterone Receptor (PR) are considered positive when expressed ≥1% on immunohistochemistry (IHC).
2. HER2 is considered negative by IHC when expression is 0 or 1+ and if equivocal 2+ then a reflex in situ hybridization should be not amplified (standard practice per ASCO/CAP criteria).
* Participants must have Presence of an ESR1 mutation detected via tissue based or blood based (ctDNA) genomic profiling.
* Participants must have been previously treated with at least 1 line of endocrine therapy and a CDK 4/6 inhibitor in the metastatic setting.
* Participants must have measurable or nonmeasurable (evaluable) disease on imaging by RECIST v1.1.
* Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
* Participants must be adults 18 years or older.
* Participants must have the ability to understand and the willingness to sign a written informed consent document.
* Participants must be able to read and speak standard English or Spanish.
* Participants must have adequate organ and marrow function as defined below:
1. absolute neutrophil count ≥1,000/mcL
2. platelets ≥75,000/mcL
d. AST(SGOT)/ALT(SGPT) ≤3 fold × institutional ULN e. creatinine 1.5 ≤ institutional ULN f. hemoglobin (Hb) ≥ 9 g/dL g. Total bilirubin \< 1.5 x ULN or \<3 x ULN in the presence of documented Gilbert's syndrome unconjugated hyperbilirubinemia)
* Participants must have a negative pregnancy test for pre-menopausal women of childbearing potential.
* Participants that are pre-menopausal women of childbearing potential who are sexually active with a male partner must agree to use adequate contraception prior to the study, for the duration of study participation.
* Inclusion of minorities: patients of all races and ethnic groups who meet the above inclusion and below exclusion criteria are eligible for this trial.
* Stated willingness to comply with all study procedures and availability for the duration of the study.
* Participants must have the ability to understand and the willingness to sign a written informed consent document or have a legally authorized representative sign on the participant's behalf.
* Participants with treated and stable brain metastases are eligible if brain imaging shows no evidence of progression within 2 months of trial enrollment.
Exclusion Criteria:
* Pregnant women are excluded from this study because study treatment agent(s) used in this study may have the potential for teratogenic or abortifacient effects. Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with agents used in this study, breastfeeding should be discontinued if the mother is treated with study agents used in this study.
* Previous treatment with Elacestrant.
* History of allergic reactions attributed to the study drugs.
* Active, progressing or newly diagnosed CNS metastases, including leptomeningeal carcinomatosis, because systemic treatment would need to be paused for these patients.
* Treatment with any investigational compound within 21 days prior to the first dose of study drugs or during this study.
* 14 day washout periods from previous anticancer therapy(ies) is required prior to enrollment including:
* Cytotoxic chemotherapy
* Tamoxifen or aromatase inhibitors
* Fulvestrant
* Targeted agents such as CDK 4/6 inhibitors, PIK3CA inhibitors, MTOR inhibitors
* Diagnosis or treatment for another systemic malignancy within 2 years before the first dose of study drugs, or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
* Uncontrolled intercurrent illness including-but not limited to-ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Patients with advanced, symptomatic visceral spread, that are at risk of life-threatening complications in the short term, including massive uncontrolled effusions (peritoneal, pleural, pericardial), pulmonary lymphangitis.
* Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome.
* Active infection including tuberculosis, hepatitis B (known positive HBV surface antigen \[HbsAg\]), or hepatitis C (HCV). Participants with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HbsAg) are eligible. Participants with positive Hepatitis C Virus (HCV) antibody are eligible if polymerase chain reaction is negative for HCV RNA.
* Concurrent or prior use of immunosuppressive medication within 14 days before the first dose of study drugs, with the following exceptions: premedication with dexamethasone, intranasal, inhaled, topical or local steroid injections, systemic corticosteroids at physiologic doses not exceeding 10 mg/day of prednisone or its equivalent; steroids as premedication for hypersensitivity reactions (e.g., premedication for iodinated contrast allergy before CT scan).
* Inability to comply with protocol requirements.
