Inclusion Criteria:

          -  Histologically confirmed ER+, PR+, HER2- metastatic or unresectable breast cancer

               -  PR positivity is defined as ≥1% expression by immunohistochemistry (IHC) on fresh
                  or archival tumor tissue

               -  Tissue samples obtained, stained, and interpreted outside of MSKCC will be
                  accepted

               -  Those patients who do not have adequate/accessible archival tissue available and
                  for whom biopsy is not a significant risk procedure may be required to consent to
                  pretreatment biopsy

          -  Completed at least 6 months (+/- 4 weeks) of first-line letrozole/palbociclib without
             radiological progression or unresolved toxicity

             °Patients who underwent dose reduction of palbociclib to 100mg daily or 75mg daily
             will be eligible if:

               1. The dose reduction was implemented ≥4 weeks prior to enrollment

               2. Patients have demonstrated resolution of all acute toxic effects of prior therapy
                  to NCI CTCAE (Version 5.0) Grade ≤ 1

          -  ctDNA-positive, defined as:

             °Presence of a tumor-derived somatic mutation in the peripheral blood using the
             MSK-ACCESS assay after 6 months of letrozole/palbociclib (+/- 4 weeks); at least one
             mutation should have avariant allele fraction of ≥ 0.5%

          -  Completed MSK IMPACT testing from primary or metastatic tissue

          -  Radiologically evaluable or measurable disease per RECIST Version 1.1

          -  Age ≥ 18 years

          -  Pre-menopausal patients are eligible as long as they are on LHRH agonist for at least
             four weeks prior to starting trial therapy and commit to continue LHRH agonist for as
             long as patient is receiving trial therapy or medical contraindications arise.

          -  Eastern Cooperative Oncology Group Performance Status (ECOG) of 1 or Karnofsky
             Performance Status (KPS) of ≥ 70%

          -  Women of child-bearing potential:

               -  Must have a negative pregnancy test within 14 days prior to commencement of study
                  treatment

               -  Agreement to remain abstinent (refrain from heterosexual intercourse) or use
                  nonhormonal contraceptive methods with a failure rate of <1% per year during the
                  treatment period and for 120 days after the last dose and agreement to refrain
                  from donating eggs during this same period

               -  Note: for women with therapy-induced amenorrhea, baseline measurements of FSH
                  and/or estradiol are needed to ensure menopausal status.

          -  Adequate hematologic and organ function demonstrated within 14 days prior to
             initiation of study treatment, defined by the following:

               -  Absolute neutrophil count ≥ 1.2K/ µL

               -  Hemoglobin ≥ 9 g/dL

               -  Platelet count ≥ 100,000/ µL

          -  Total bilirubin ≤ 1.5 x ULN

          -  Serum albumin ≥ 2.5 g/dL

          -  AST and ALT ≤ 2.5 x ULN

          -  Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min on the basis of the
             Cockcroft-Gault glomerular filtration rate estimation

          -  INR < 1.5 x ULN and aPTT < 1.5 x ULN

             °For patients requiring anticoagulation therapy with warfarin, a stable INR between
             2-3 is required. If anticoagulation is required for a prosthetic heart valve, then
             stable INR between 2.5-3.5 is permitted.

          -  At least 4 weeks post-op from any major surgical procedure

          -  Patients with asymptomatic brain metastases which have been treated with surgery or
             radiation and demonstrate stability for ≥ 3 months will be allowed

          -  Able to swallow tablets whole, without crushing

        Exclusion Criteria:

          -  Radiologic disease progression while on treatment with letrozole and palbociclib in
             the first line prior to enrollment

          -  History of another invasive malignancy (other than non-melanoma skin cancer or
             curatively treated in situ carcinoma) with evidence of disease within the past 3 years

          -  Any psychological, familial, sociological or geographic condition that would
             potentially hinder compliance with the study protocol

          -  Known untreated or symptomatic brain metastasis

          -  Uncontrolled hypertension (systolic BP ≥ 160 mmHg or diastolic BP ≥ 95mmHg) despite
             medical treatment. Patients with a history of hypertension are allowed provided blood
             pressure is controlled by anti-hypertensive treatment.

          -  Clinically significant heart disease as evidenced by myocardial infarction or arterial
             thrombotic event within the past 6 months, severe or unstable angina, or New York
             Heart Association (NYHA) Class II-IV heart disease or cardiac ejection fraction
             measurement of < 50% at baseline

          -  Screening ECG with rate-corrected (using Friderica's correction) QT interval (QTcF) of
             >480 msec or a history of cardiac arrythmias

          -  Refractory nausea and vomiting, requirement for parenteral hydration and/or nutrition,
             drainage gastrostomy tube, malabsorption, external biliary shunt, or significant small
             bowel resection that would preclude adequate study drug absorption

          -  Is pregnant or breastfeeding, and/or expecting to conceive within the projected
             duration of the trial, starting with the pre-screening or screening visit through 120
             days after the last dose of trial treatment.

          -  Current use of estrogen or progesterone products including intrauterine and
             implantable contraceptive devices.

          -  Anticipated or ongoing administration of anti-cancer therapies other than those
             administered in this study

          -  Active Hepatitis B (HBsAg positive or hepatitis B virus DNA≥1×10^3 copy/ml) or
             Hepatitis C (e.g., HCV RNA [qualitative] is detected).

          -  Use of any prescription medication during the prior 28 days of first onapristone
             dosing that the investigator judges is likely to interfere with onapristone activity;
             specifically, strong inhibitors or inducers, or sensitive substrates of cytochrome
             P450 CYP3A4.