Estradiol in Treating Patients With ER Beta Positive, Triple Negative Locally Advanced or Metastatic Breast Cancer

Prior treatment

• PRE-REGISTRATION CRITERIA: Deep vein thrombosis / pulmonary embolism (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).
• PRE-REGISTRATION CRITERIA: Stroke =\< 6 months prior to pre-registration.
• PRE-REGISTRATION CRITERIA: Two or more episodes of DVT and/or PE =\< 5 years prior to pre-registration.
• PRE-REGISTRATION CRITERIA: Abnormal uterine bleeding =\< 6 months prior to pre-registration
• PRE-REGISTRATION CRITERIA: 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 CRITERIA: None of the following therapies are allowed =\< 14 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 (exceptions for alopecia).

Other illness

• PRE-REGISTRATION 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).
• PRE-REGISTRATION CRITERIA: History of coagulopathy.

• PRE-SCREENING CRITERIA (STEP 0): Women of age \>= 18 years
• PRE-SCREENING CRITERIA (STEP 0): History of locally advanced or metastatic breast cancer that is ERalpha negative or low (\< 1% nuclear staining) and HER2 negative.
  • Note: HER2 negative disease per 2018 American Society of Clinical Oncology/College of American of Pathologists (ASCO/CAP) guidelines, one of the following must apply:
  • 0 or 1+ by immunohistochemistry (IHC) and not amplified by in situ hybridization (ISH);
  • 0 or 1+ by IHC and ISH not done;
  • 2+ by IHC and ISH results are: \< 6.0 HER2 signals/cell with HER2/CEP17 ratio \< 2.0;
  • IHC not done and not amplified by ISH.
• PRE-SCREENING CRITERIA (STEP 0): =\< 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).
• PRE-SCREENING CRITERIA (STEP 0): Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• PRE-SCREENING CRITERIA (STEP 0): Willing to submit a biopsy specimen from locally recurrent or metastatic site (or primary if metastatic site not available) of breast cancer for ERbeta staining to Mayo Clinic Anatomic Pathology.
• PRE-SCREENING CRITERIA (STEP 0): No prior history of metastatic ERalpha positive breast cancer (\>= 1%)
• PRE-REGISTRATION CRITERIA (STEP 1): Presence of moderate or strong nuclear ERbeta staining in \> 25% of cells in specimen submitted during Pre-Screening Step.
• PRE-REGISTRATION CRITERIA (STEP 1): For patients who did not have a biopsy or lacking ERalpha, progesterone receptor (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 ERalpha, PR, and HER2 as well as additional research cores.
• PRE-REGISTRATION CRITERIA (STEP 1): Measurable or non-measurable disease as defined by Response Evaluation Criteria in Solid Tumors (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 nor a target lesion.
• PRE-REGISTRATION CRITERIA (STEP 1): 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.
• PRE-REGISTRATION CRITERIA (STEP 1): ECOG performance status 0 or 1.
• PRE-REGISTRATION CRITERIA (STEP 1): =\< 3 prior chemotherapy regimens for treatment of metastatic breast cancer.
  • NOTE: Prior use of monoclonal antibodies targeting PD1, PDL1 is allowed.
• PRE-REGISTRATION CRITERIA (STEP 1): 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.
• PRE-REGISTRATION CRITERIA (STEP 1): Able to swallow oral medications.
• PRE-REGISTRATION CRITERIA (STEP 1): 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.
• REGISTRATION CRITERIA (STEP 2): For patents who had a biopsy taken from a metastatic site =\< 12 months prior to Pre-Registration: Confirmation from the local lab that the tumor from this biopsy was ERalpha negative (\< 1% nuclear staining) and HER2 negative
• REGISTRATION CRITERIA (STEP 2): For patients who underwent a pre-registration biopsy: Histologic confirmation from local lab that tumor is ERalpha negative (\< 1% nuclear staining), and HER2 negative
• REGISTRATION CRITERIA (STEP 2): Hemoglobin \>= 8 g/dL (=\< 14 days prior to registration).
• REGISTRATION CRITERIA (STEP 2): Platelet count \>= 75,000/mm\^3 (=\< 14 days prior to registration).
• REGISTRATION CRITERIA (STEP 2): Creatinine =\< 1.5 x upper limit of normal (ULN) (=\< 14 days prior to registration).
• REGISTRATION CRITERIA (STEP 2): Total bilirubin =\< 1.5 x ULN (=\< 14 days prior to registration).
• REGISTRATION CRITERIA (STEP 2): Aspartate aminotransferase/serum glutamic-oxaloacetic transaminase (AST/SGOT) =\< 2.5 x ULN (=\< 14 days prior to registration).
  • For patients with liver metastasis =\< 5 x ULN.