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

This is an interventional treatment trial for Advanced Triple-Negative Breast Carcinoma Read More

Inclusion Criteria:

• 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.

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).