The goal of the first part of this clinical research study is to find the highest tolerable dose of TPI-287 in patients with breast cancer that has spread to the brain.

The goal of the second part of this study is to learn if TPI-287 can control breast cancer that has spread to the brain. The safety of this drug will also be studied.

The Study Drug:

TPI-287 is designed to prevent cancer cells from dividing, which may slow and/or stop the growth of cancer cell.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will receive, TPI 287 by vein over 60 minutes on Day 1 of every 21 day cycle.

Before you receive the study drug, you will receive dexamethasone by mouth, Benadryl (diphenhydramine HCL) by vein over 30-60 minutes, and ranitidine over 30-60 minutes to help prevent a potential serious allergic reaction.

Study Visits:

At all study visits, you will be asked about any side effects you may be having and about any other drugs you may be taking.

On Days 1, 8, and 15 of Cycle 1, blood (about 2-3 teaspoons) will be drawn for routine tests. If you are taking coumadin, blood (about 1-2 teaspoons) will be drawn to check how well your blood clots.

On Day 1 of Cycle 1, your performance status will be recorded and your vital signs will be measured.

Within 7 days of Day 1 of Cycles 2 and beyond:

• Blood (about 2-3 tablespoons) will be drawn for routine tests. If you are taking coumadin, blood (about 1-2 teaspoons) will be drawn to check how well your blood clots.
• You will have a physical exam, including measurement of your weight and vital signs.
• Your performance status will be recorded.
• You will have a neurological exam.

Every 6 weeks (that is, before each odd-numbered cycle):

• You may have CT scans or MRI scans of the chest, abdomen, and pelvis to check the status of the disease.
• You will have a MRI of your brain. The MRI will require a catheter to be inserted into one of your veins in order to inject the MRI contrast agent.

The study doctor and staff will review your imaging scans to check what stage of disease the tumors inside and/or outside your brain are.

Length of Study:

You may continue to receive TPI 287 for as long as the doctor thinks it is in your best interest. You will no longer be able to receive TPI 287 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 you have completed the end-of-treatment and follow-up visits.

End-of Treatment Visit:

About 4 weeks after you stop taking TPI 287:

• You will have a physical exam, including measurement of your vital signs.
• You will have a neurological exam.
• Your performance status will be measured.
• Blood (about 2 tablespoons) will be drawn for routine tests.
• You will have a CT and/or MRI to check the status of the disease. This may include a brain MRI. If your doctor thinks it is needed, you will have a bone scan.
• You will be asked about any side effects you may have had any drugs you may be taking.

Follow-Up Visits:

Once you are off-study, you will be contacted either in the clinic or by phone every 3 months for up to 1 year after you enrolled on the study to check on the status of your health. If you are called, it will take less than 5 minutes.

This is an investigational study. TPI 287 is not FDA approved or commercially available. At this time, TPI 287 is being used in research only.

Up to 69 patients will take part in this study. All will be enrolled at MD Anderson.

Inclusion Criteria:

1. Patients must have histologically proven breast cancer with metastatic disease to the brain.
2. Patients must have measurable disease on MRI that has progressed after prior therapy. PD will be defined as a>/= 25% increase in the sum of the products of greatest perpendicular diameters of all measurable disease over the smallest sum observed (since treatment started) on Gd-MRI, the appearance of new lesions on scan, or clinical or neurologic worsening despite stable disease on the last 2 scans.
3. Patients may have had any number of prior surgeries, radiation and/or chemotherapy regimens as adjuvant, neoadjuvant or palliative therapy for the treatment of their disease
4. Patients must be >/=18 years of age.
5. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0,1 or 2.
6. Patients must have adequate bone marrow function as evidenced by an absolute neutrophil count >/=1,500/microliters and a platelet count >/=100,000/microliter, adequate renal function as evidenced by serum creatinine </=2.0 mg/dL, adequate hepatic function as evidenced by serum total bilirubin </=2.0 mg/dL, AST/serum glutamate oxaloacetate transaminase (SGOT) and ALT/serum glutamate pyruvate transaminase (SGPT) </= 3X the upper limit of normal (ULN).
7. Patients must have recovered and healed from the effects of any prior surgery, must have received prior chemotherapy at least 2 weeks prior to dosing with adequate recovery of white blood cell count (WBC) and platelet counts, and at least 12 weeks must have elapsed from the completion of radiotherapy, unless there are new lesions appearing on imaging within this 12 weeks frame.
8. Women of child-bearing potential (i.e. </= 50 years of age or has had menstrual cycle within the past 12 months, if > 50 years of age. If in doubt, check FSH, LH and estradiol level) must have a negative urine or serum pregnancy test at screening.
9. Sexually active patients must agree to use adequate contraception (abstinence or barrier contraceptives must be used throughout the trial and one month after end of treatment) for the duration of the study .
10. Patients or their legal representative must be able to read, understand and sign an informed consent form (ICF).
11. TPI 287 may interfere with coumadin dosing and patients who are taking this combination will require monitoring of their PT, PTT and international normalized ratio (INR).

Exclusion Criteria:

1. Patients who are receiving concurrent enzyme-inducing anti-epileptic drugs (EIAEDs) (e.g., carbamazepine, oxcarbazepine, phenytoin, fosphenytoin, phenobarbital and primidone) or who received EIAEDs within 2 weeks prior to the first dose of study drug.
2. Patients with uncontrolled intracranial hypertension syndrome (defined as: persistence of headache, transient visual obscurations, and/or diplopia despite optimal clinical management) or uncontrolled seizure activity (i.e. recorded despite optimal medical management).
3. Patients who are not on a stable or decreasing steroid dose for the previous week prior to the first dose of study enrollment
4. Patients who are taking bevacizumab or have taken bevacizumab within the past 2 weeks for treatment of their brain metastases
5. Patients with an active infection (i.e., clinical signs or symptoms, including, but not limited to: bleeding/pustulant skin infections; productive cough associated with fever) on antibiotics or with a fever >/=38.5°C within 3 days prior to registration (i.e. date when the patient signs the consent and/or the patient is registered in CORE).
6. Patients with New York Heart Association (NYHA) Class 3 or 4 congestive heart failure.
7. Patients with known HIV or Hepatitis B or C
8. Patients who are pregnant or lactating or not practicing adequate contraception
9. Patients with any other medical condition, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with the patient's ability to sign the ICF or his/her ability to cooperate and participate in the study, or to interfere with the interpretation of the results.
10. Patients who are receiving concomitant systemic therapy for breast cancer.
11. Patients with leptomeningeal disease (LMD) or with a history of LMD will be excluded.

All patient's enrolled in the study were analyzed (Intention To Treat)

Collected every 28 days with an average of up to a year.