Inclusion Criteria:

- HER-2 negative advanced or metastatic breast cancer

- Disease has become worse after at least 1 prior chemotherapy regimen for advanced or
metastatic disease

- Advanced or metastatic disease resistant to both a taxane and an
anthracycline-containing chemotherapy regimen, or resistant to taxanes and for whom
further anthracycline therapy is not indicated

- Patients with controlled brain metastases must have finished receiving radiation
therapy and if on corticosteroids, be on a stable or tapering dose of ≤ 10 mg/day of
prednisone or equivalent for at least 28 days prior to study entry

- Measurable disease

- Female 18 years of age or older

- Performance status less than or equal to 2

- Life expectancy of more than 3 months

- Blood, liver and kidney laboratory test results that meet protocol requirements

- Patients must have a negative serum pregnancy test within 14 days before enrollment
and agree to use medically acceptable and effective birth control from enrollment
until at least 30 days after the last dose of pralatrexate. Patients who are
postmenopausal for at least 1 year (more than 12 months since last menses) or are
surgically sterilized do not require this test.

- Willing to attend visits for repeat dosing and follow up

- Give written informed consent

Exclusion Criteria:

- Patients with only bone metastasis

- Patients with a single metastatic site without histological proof that the lesion is
metastatic breast cancer

- Patients with inflammatory breast cancer

- Treatment with systemic chemotherapy, hormone therapy, radiation therapy, or other
investigational therapy within 3 weeks (6 weeks for nitrosoureas, mitomycin C) prior
to enrollment, except for the following:

- Bisphosphonates, if ongoing

- Prior treatment with methotrexate

- Prior treatment with anti-angiogenics within 6 months prior to enrollment

- Have received more than 2 prior chemotherapy regimens (more than 3 if one of the
treatments was neoadjuvant or adjuvant chemotherapy)

- Have previously received pralatrexate

- Have received more than the allowed maximum total dose of anthracycline

- Prior radiation therapy on more than 30% of bone marrow reserve or prior bone
marrow/stem cell transplantation

- Congestive heart failure Class III/IV

- Uncontrolled hypertension (high blood pressure)

- Active infection or any serious medical condition, which would impair the ability of
the patient to receive protocol treatment

- Females who are pregnant or breastfeeding

- Major surgery within 14 days of enrollment

- Another active cancer in addition to advanced or metastatic breast cancer, except
well treated in situ cervical cancer and basal cell skin cancer

- Dementia or other altered mental status that would prevent the patient from
understanding and giving informed consent or limit her ability to follow the study
requirements

- Patients who are human immunodeficiency virus (HIV)-positive and have a CD4 count of
less than 100 mm3 or detectable viral load within past 3 months and is receiving
anti-retroviral therapy

- Patients with hepatitis B virus (HBV) or hepatitis C virus (HCV) who have a
detectable viral load or immunological evidence of chronic active disease or
receiving/requiring antiviral therapy