Age >= 18 years

Age

Histologic proof of metastatic breast cancer that is unresected at registration (with no intention of resecting tumors during this study). Evidence of metastatic breast cancer confirmed by radiological imaging

Measurable disease (see Section 11.21 for definition of measurable disease)

Metastatic site(s) must be amenable to biopsy

Post-menopausal according to any one of the following criteria: a. Age >60 years old b. Age >45 years old with last menstrual period >12 months prior to registration and estriadiol and folliclestimulating hormone (FSH) levels in postmenopausal range (per institutional normal limits) c. Bilateral oophorectomy If male (check NA).

Tumor estrogen, progesterone and HER2 [tested by IHC or FISH (fluorescent in situ hybridization)] status from the metastatic site. If not available, the results from the original tumor diagnosing the primary breast cancer may be used.- Triple negative disease only [ER- (defined as =<1% by IHC), PR- (defined as =<1% by IHC), and HER2-] Patients with triple negative breast cancer are allowed if there is clinical or radiographic evidence of tumor progression in the adjuvant or metastatic setting. (Note: If HER2 result by IHC is 2+ equivocal, the tumor must be confirmed to be HER2- by FISH.)

Prior treatments allowed: 0 or 1 prior chemotherapy regimens for breast cancer. <=2 prior aromatase inhibitor regimens (including letrozole)

The following laboratory values obtained <= 14 days prior to registration

Earliest laboratory test date (Note: These dates pertain to the following labs only.)

Latest laboratory test date (Note: These dates pertain to the following labs only.)

ANC >= 1,500/mm^3

ANC

Platelet count >= 100,000/mm^3

Peripheral Platelet Count

Total bilirubin =< upper limit of normal (ULN)

Total Bilirubin

Total bilirubin ULN

SGPT (ALT) <=3 x ULN or SGPT (ALT) <=5 x ULN if elevations are due to liver metastasis

Is there liver involvement

SGPT (ALT) (<=5 x ULN if evalations are due to liver metastasis - <=3 x ULN)

SGPT (ALT) ULN

SGOT (AST) <=3 x ULN or SGOT (AST) <=5 x ULN if elevations are due to liver metastasis

SGOT (AST) (<=5 x ULN if evalations are due to liver metastasis - <=3 x ULN)

SGOT (AST) ULN

TSH <= ULN

TSH

TSH ULN

Creatinine <= 1.5 x ULN

Creatinine

Creatinine ULN

ECOG performance status (PS) 0, 1, or 2

ECOG performance status grade

Ability to provide informed written consent

Willing to return to NCCTG enrolling institution for follow-up

Life expectancy >=12 weeks

Willing to provide tissue samples for correlative research purposes (see Sections 4.0, 6.25, and 17.1)

Known standard therapy for the patient's disease that is potentially curative or definitely capable of extending life expectancy

>1prior chemotherapy regimen for breast cancer. >2 prior aromatase inhibitor regimens

Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

Chemotherapy <=4 weeks prior to registration (Any of the following prior therapies: If no prior chemotherapy check NA)

Last day of chemotherapy (If prior chemotherapy)

Radiation therapy <=4 weeks prior to registration (If no prior radiation therapy check NA)

Last day of radiation therapy (If prior radiation therapy)

Radiation to >25% of bone marrow

Failure to fully recover from acute, reversible effects of prior chemotherapy regardless of interval since last treatment

New York Heart Association class III or IV cardiovascular disease

Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown. - Pregnant women - Nursing women - Men or women of childbearing potential who are unwilling to employ adequate contraception (as determined by the treating physician)

Receiving any other investigational agent concurrently which would be considered as a treatment for the primary neoplasm

Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens

Immunocompromised patients (other than that related to the use of corticosteroids) including patients known to be HIV positive

History of other malignancy <=5 years with the exception of non-melanoma skin cancer or carcinoma in-situ of the cervix

History of myocardial infarction or unstable angina <=6 months prior to registration or congestive heart failure (CHF) requiring use of ongoing maintenance therapy, or life-threatening ventricular arrhythmias

Receiving CYP3A4 inhibitors and inducers or any other contraindicated agent listed in Appendix III

Congenital long QT syndrome or QTcF>450 msec on screening ECG:- Complete left bundle block or use of a permanent cardiac pacemaker, history or presence of ventricular tachyarrhythmias, clinically significant resting bradycardia (<50 beats per minute)- Right bundle branch block + left anterior hemiblock (bifascicular block

Consent form signed and dated

Date Informed Consent Signed

Authorization for use and disclosure of protected health information signed and dated (Non-USA institution only check NA)

Date of authorization

A mandatory correlative research component is part of this study for all patients, the patient will be automatically registered onto this component (see Section 3.19c, 4.0 and/or 17.1)

Treatment on this protocol must commence at the accruing membership under the supervision of an NCCTG member physician

Treatment cannot begin prior to registration and must begin <=14 days after registration

Pretreatment tests/procedures must be completed <= 14 days prior to registration (see Section 4.0 - NOTE: The earliest pretreatment test/procedure date must be less than or equal to the earliest laboratory test/procedure date and the latest pretreatment test/procedure date must be greater than or equal to the latest laboratory test/procedure date.)

Earliest pretreatment test/procedure date

Latest pretreatment test/procedure date

All required baseline symptoms (see Section 10.3) must be documented and graded

Study drug availability checked

Blood draw kit availability checked (Blood kit must be available on site)

Patient has given permission to give his/her blood sample for research testing

Patient has given permission to store and use his/her blood/plasma sample for future research to learn about, prevent, or treat cancer

Patient has given permission to store and use his/her blood/plasma sample for use in future research to learn about, prevent, or treat other health problems (for example: diabetes, Alzheimer's disease, or heart disease)

Patient has given NCCTG permission to give blood to outside researchers

Patient has given permission to store and use his/her sample(s) for use in future research to learn about, prevent, or treat cancer

Patient has given permission to store and use his/her tissue(s) sample for use in future research to learn about, prevent, or treat other health problems (for example: diabetes, Alzheimer's disease, or heart disease)

Patient has given NCCTG permission to give tissue(s) to outside researchers

Is this an NCCTG institution (NCCTG Institutions only: N0932 must be open at site and offered to patient. - This question may be answered yes or no.)

Patient has agreed to be enrolled on N0932 (At time of registration, the following will be recorded:)

Grouping Factor (Patient Cohort)