Inclusion Criteria:

- Histologically confirmed breast adenocarcinoma that is metastatic. Receptor status of
the tumor must be known.

- Disease progression during or after immediate previous therapy, or intolerable
toxicity leading to cessation of immediate previous therapy

- Previous treatment for MBC:

- AT Cohort: Prior AT required as adjuvant or metastatic therapy; no more than 2
prior chemotherapy regimens for MBC.

- ATX Cohort: Prior ATX required as adjuvant or metastatic therapy;no more than 4
prior chemotherapy regimens for MBC.

- For patients with positive receptor status:

- Patients with HER2+ MBC must have received prior trastuzumab.

- Patients with ER+ MBC must have received prior hormone therapy.

- Measurable disease by RECIST Version 1.1

- Women 18 years or older

- ECOG performance status of 0 to 2

- Adequate bone marrow, renal and hepatic functions

Exclusion Criteria:

- Major surgery within 3 weeks before study start

- Known or suspected brain metastases requiring intervention with steroids and/or
radiation therapy

- Prior chemotherapy, immunotherapy, non-investigational agent, or other therapy used
to treat the cancer within 3 weeks before scheduled administration of EZN-2208

- History of other primary cancer within 5 years of enrollment, unless

1. Curatively resected non-melanomatous skin cancer, or

2. Curatively resected cervical cancer

- Lack of recovery to Grade 1 from any reversible side effects related to the
administration of an investigational agent, chemotherapy, or other prior treatments
for the cancer

- Current participation in another clinical study with an investigational agent and/or
use of an investigational drug (not including investigational use of an approved
drug) in the 30 days before the first administration of EZN-2208

- Known chronic infectious disease, such as AIDS