Phase IIB Neoadjuvant Enzalutamide (ZT) Plus Taxol for Androgen Receptor (AR)-Positive Triple-Negative Breast Cancer (AR+ TNBC)

Study Drug Administration:

If you are found eligible to take part in this study, you will take enzalutamide by mouth
every day for 12 study cycles. Each cycle is 7 days (1 week).

On Day 1 of each cycle, you will receive paclitaxel by vein over about 2 hours.

If you have side effects, the study doctor may decide to lower your study drug dose level or
have you stop taking the drug for a short time. If your dosing is stopped, you may be able to
restart the study drug later at the same dose or a lower dose. The study doctor will discuss
this with you.

Study Visits:

Before treatment begins, blood (about 2 teaspoons) will be collected for biomarker testing
(including genetic biomarkers). Biomarkers are found in the blood/tissue and may be related
to your reaction to the study drug.

On Day 1 of each cycle:

°Blood (about 2 teaspoons) will be drawn for routine tests.

On Day 1 of Cycles 1, 5 & 9:

°You will have a physical exam and your weight, vital signs, and performance status will be
recorded.

On Day 1 of Cycle 7, blood (about 2 teaspoons) will be drawn for CTC and biomarker tests.

Any time during the 12 study cycles, you may have imaging scans (the same ones that were
performed at Screening) to check the status of the disease, if the doctor thinks they are
needed.

At the end of 12 cycles:

- You will have a physical exam.

- Blood (about 4 teaspoons) will be drawn for routine tests, CTC tests, and biomarker
testing.

- You will have imaging scans of the breast and lymph nodes to check the status of the
disease.

After 12 cycles of study drugs on this study, you may then have surgery to remove the
tumor(s). You will be given a surgery consent form that describes the procedure and its
risks. If you do not have surgery, you may still have a lymph node biopsy or removal, based
on standard care. Your doctor can discuss this with you.

Leftover tissue/blood from study testing will be banked at MD Anderson. Before your samples
can be used for research, the researchers must get approval from the Institutional Review
Board (IRB) of MD Anderson. The IRB is a committee of doctors, researchers, and community
members. The IRB is responsible for protecting study participants and making sure all
research is safe and ethical.

Your samples will be given a code number. No identifying information will be directly linked
to your samples. Only the researcher in charge of the bank will have access to the code
numbers and be able to link the samples to you. This is to allow medical data related to the
samples to be updated as needed.

Length of Treatment:

You may receive up to 12 cycles of chemotherapy. You will no longer be able to take the study
drugs if the disease gets worse, if intolerable side effects occur, or if you are unable to
follow study directions.

Your participation on the study will be over after the follow-up visit.

Follow-Up:

Within 30 days (+/- 3 days) after surgery/biopsy, you will have a follow-up visit. During
this visit, you will be asked about how you are doing, and blood (about 2 teaspoons) will be
drawn for routine tests.

Inclusion Criteria:

1. Patients must be willing to sign the protocol-specific written informed consent.

2. Patients with histologically confirmed intact primary cancer that is confirmed
invasive carcinoma of the breast with at least 1.0 cm of residual disease as measured
by mammography, ultrasound, or breast MRI after neoadjuvant anthracycline based
chemotherapy.

3. Patients must have triple-negative breast cancer defined as ER<10%; PR<10% by
immunohistochemistry (IHC) and HER2 0-1+ by IHC or 2+, FISH non-amplified.

4. Androgen Receptor will be quantified using a CLIA-compliant assay for AR on a biopsy
specimen obtained prior to the start of treatment. AR- positivity is defined as >/=
10% of nuclear staining.

5. Patient's disease state must be AJCC 7th edition stage I-III.

6. Men or women must be 18 years of age or older.

7. Patients must have a performance status of 0 - 1 on the ECOG performance scale.

8. A negative serum or urine pregnancy test must be done within 72 hours before the first
dose of the study medication for women of childbearing potential as per institutional
guidelines. Post-menopausal women (defines as no menses for at least 1 year) and
surgically sterilized women are not required to undergo pregnancy test.

9. Men on study must use a condom if having sex with a pregnant woman.

10. Male patients and his female partner who is of childbearing potential must use 2
acceptable methods of birth control (one of which must include a condom as a barrier
method of contraception) starting at screening and continuing throughout the study
period and for 3 months after final study drug administration.

11. Patient must have adequate organ function as determined by the following laboratory
values: 1) Absolute neutrophil count >/= to 1,500 /uL 2) Platelets >/= to 100,000 / uL
3) Hemoglobin >/= to 9 g/dL 4) Creatinine clearance >/= to 50 ml/min 5) Total
bilirubin aminotransferase (AST)
Exclusion Criteria:

1. Patients who have received previous antitumor therapies (other than
anthracycline-based neoadjuvant chemotherapy for the current cancer event).

2. Breast-feeding at screening or planning to become pregnant during the course of
therapy.

3. Patients who have had major surgery within 21 days before Cycle 1, Day 1.

4. Patients with a known history of hypersensitivity to paclitaxel that did not resolve
with pre- medication.

5. Patients with left ventricular ejection fraction <50% or 10% decrease from baseline on
echocardiogram after anthracycline based chemotherapy.

6. Patients with gastrointestinal impairment that would affect the absorption of
Enzalutamide or previous history of colitis.

7. Subjects requiring daily corticosteroids, other than those given as premedication for
the anthracycline-based chemotherapy.

8. Patients with known or suspected brain metastasis or active leptomeningeal disease.

9. History of seizure or any condition that may predispose to seizure (e.g., prior
cortical stroke, significant brain trauma) at any time in the past. Also, history of
loss of consciousness or transient ischemic attack within 12 months of Day 1 visit.

10. Myocardial infarction within 6 months before starting therapy, symptomatic congestive
heart failure (New York Heart Association > class II), unstable angina, or unstable
cardiac arrhythmia requiring medication.