Pre-Screening Inclusion Criteria:

• Women of age ≥ 18 years old.
• History of locally advanced or metastatic breast cancer that is ERα negative (<1% nuclear staining) and HER2 negative (see note below).
  • Note: HER2 Negative Disease per 2013 ASCO/CAP guidelines, 8one of the following must apply:
    • 0 or 1+ by IHC and not amplified by ISH;
    • 0 or 1+ by IHC and ISH not done;
    • 2+ by IHC and and ISH results are: < 6.0 HER2 signals/cell with HER2/CEP17 ratio < 2.0;
    • IHC not done and not amplified by ISH.
• ≤ 3 prior chemotherapy regimens for treatment of metastatic breast cancer.
  • Note: Prior use of monoclonal antibodies targeting PD1, PDL1 is allowed(if administered as monotherapy it is not counted as a chemotherapy regimen).
• ECOG Performance status 0 or 1.
• Willing to submit a biopsy specimen from locally recurrent or metastatic site (not primary) of breast cancer for ERβ staining to Mayo Clinic Anatomic Pathology.

Pre-Registration Inclusion Criteria:

• Presence of moderate or strong nuclear ERβ staining in >25% of cells in specimen submitted during Pre-Screening Step.
• For patients who did not have a biopsy or lacking ERα, PR, and HER2 results from a locally advanced or metastatic site performed ≤12 months prior to Pre-Registration:
  • Willing to undergo a standard of care biopsy of locally recurrent or metastatic breast cancer for ERα, PR, and HER2 as well as additional research cores.
• Measurable or non-measurable disease as defined by RECIST criteria that will be assessed using imaging-based evaluations.
  • Note: The tumor lesion biopsied during the pre-registration period is not considered measurable disease or a target lesion.
• If history of brain metastases must meet the following criteria:
  • Patients with a history of brain metastases are eligible only if they are asymptomatic and have stable disease for ≥ 3 months, including < 28 days of prior to pre-registration;
  • Not receiving steroids for brain metastases.
• ECOG Performance status 0 or 1.
• ≤ 3 prior chemotherapy regimens for treatment of metastatic breast cancer.
  • Note: Prior use of monoclonal antibodies targeting PD1, PDL1 is allowed.
• Women must be postmenopausal.
  • Note: Postmenopausal status is verified by:
    • Prior bilateral surgical oophorectomy; or
    • Age ≥ 60 years; or
    • Age < 60 years with no menses for >1 year with estradiol levels within postmenopausal range, according to institutional standard.
• Able to swallow oral medications.
• Willingness to stop use of strong inducers or inhibitors of CYP3A4 prior to registration.
  • Note: Use of strong inducers or inhibitors is allowed during Pre-Registration as long as patient will complete course prior to Registration.

Pre-Registration Exclusion Criteria:

• Uncontrolled intercurrent illness including, but not limited to:
  • Ongoing or active infection;
  • Symptomatic congestive heart failure;
  • Unstable angina pectoris;
  • Uncontrolled symptomatic cardiac arrhythmia;
  • Uncontrolled hypertension (defined as blood pressure > 160/90).
• Any of the following co-morbid conditions:
  • DVT/PE ≤12 months prior to pre-registration;
    • Note: Patients who are on anticoagulant therapy for maintenance are eligible as long as the DVT and /or PE occurred > 6 months prior to Pre-Registration, and there is no evidence for active thrombosis (either DVT or PE).
  • Stroke ≤ months prior to pre-registration;
  • Two or more episodes of DVT and/or PE ≤ years prior to pre-registration;
  • Abnormal uterine bleeding ≤ 6 months prior to pre-registration;
  • History of coagulopathy.
• Other active second malignancy other than non-melanoma skin cancers within 3 years prior to pre-registration.
  • Note: A second malignancy is not considered active if all treatment for that malignancy is completed and the patient has been disease-free for ≥ 3 years prior to pre-registration.

Registration Inclusion Criteria:

• For patents who had a biopsy taken from a metastatic site ≤ 12 months prior to Pre-Registration: Confirmation from local lab that tumor is ERα negative (< 1% nuclear staining), and HER2 negative
• For patients who underwent a pre-registration biopsy: Histologic confirmation from local lab that tumor is ERα negative (< 1% nuclear staining), and HER2 negative (see prior note in Pre-Screening Inclusion) .
• Laboratory values ≤ 14 days prior to registration:
  • Hemoglobin ≥ 8 g/dL;
  • Platelet Count ≥ 75,000/mm^3;
  • Creatinine ≤ 1.5 x upper limit of normal ULN;
  • Total Bilirubin ≤ 1.5 x upper limit of normal (ULN);
  • AST/SGOT ≤ 2.5 x upper limit of normal (ULN)*
    • *For patients with liver metastasis: ≤ 5 x upper limit of normal (ULN).

Registration Exclusion Criteria:

• None of the following therapies are allowed ≤ 4 days prior to registration*:
  • Chemotherapy;
  • Immunotherapy;
  • Biologic therapy;
  • Hormonal therapy;
  • Monoclonal antibodies;
  • Anti-HER2 or other "targeted" (e.g., mTOR) therapy.
  • *Note: Any adverse events derived from these therapies must be ≤ Grade 2 prior to starting study therapy (exception: alopecia).