Inclusion Criteria:
* Subject must be female and \> 18 years of age.
* Subject must be diagnosed with adenocarcinoma of the breast.
* Subject must have metastatic disease or locally recurrent disease that is not amenable to surgical resection with curative intent.
* No prior chemotherapy for locally recurrent or metastatic breast cancer.
* At least 12 months since prior adjuvant or neoadjuvant chemotherapy (including prior taxane therapy and prior anti-angiogenic therapy \[i.e. bevacizumab or a TKI\]).
* No HER-2 -over-expression (3+) breast cancer (unless treated with trastuzumab or lapatinib).
* Subject has measurable disease by RECIST criteria (randomized portion only).
* Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-1.
* Subject must have adequate bone marrow, renal and hepatic function.
* Subject must have PTT \< 1.5 x ULN and INR \< 1.5.
Exclusion Criteria:
* Subject has received anti-cancer therapy (other than chemotherapy) including investigational agents, or biologic therapy within 21 days or within a period defined by 5 half lives, whichever is shorter, prior to Study Day 1.
* Subject has not recovered to less than or equal to grade 1 clinically significant adverse effects/toxicities of the previous therapy.
* Subject has received radiation therapy within 14 days of Study Day 1.
* Subject has received anti-cancer hormonal therapy within 14 days of Study Day 1.
* Subject has undergone major surgery within 21 days of Study Day 1.
* The subject has untreated brain or meningeal metastases.
* Subject is receiving therapeutic anticoagulation therapy.
* Subject has a history of or currently exhibits clinically significant cancer related events of bleeding (e.g., hemoptysis).
* Subject currently exhibits symptomatic or persistent, uncontrolled hypertension.
* Subject has a history of myocardial infarction, stroke, or transient ischemic attack (TIA) within 6 months of study day 1.
* Subject has a documented left ventricular (LV) ejection fraction \< 50%
* Subject has known autoimmune disease with renal involvement.
