Ensayos clínicos

Inclusion Criteria:

- 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-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.

Exclusion Criteria:

- 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: 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: History of coagulopathy.

- 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).