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 index measurable lesion(s) 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 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/SGOT and ALT/SGPT </= 3X the ULN.
7. Patients must have recovered from the effects of any prior surgery, radiotherapy or other chemotherapy at least 2 weeks, and at least 12 weeks must have elapsed from the completion of radiotherapy, unless in the case 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 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 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).
5. Patients who are taking bevacizumab or have taken bevacizumab within the past 2 weeks for treatment of their brain metastases
6. Patients with 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.