This open-label, dose-finding, multi-center study is designed to determine the safety and the maximum tolerated dose of AMG 706 given once daily in combination with either weekly paclitaxel (Arm A) or once-every-3 week docetaxel (Arm B) in subjects with locally recurrent or metastatic breast cancer. Secondarily, this study will evaluate the pharmacokinetic (PK) profile of AMG 706 in both treatment arms, the PK profile of paclitaxel in Arm A and the PK profile of docetaxel in Arm B. Additionally, this study will assess objective tumor response and duration of response. Exploratory endpoints include the investigation of potential biomarker development and to assess the effects of genetic variation in drug metabolism genes, cancer genes and drug target genes on subject response to AMG 706 in combination with paclitaxel or docetaxel.

Inclusion Criteria:

• Histologically or cytologically confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Female 18 years of age or older.
• Adequate hematologic, renal and hepatic function.
• Competent to comprehend, sign, and date an IRB-approved informed consent form.
• Subjects of childbearing potential and sexually active must provide a negative pregnancy test and use accepted and effective method of contraception.

Exclusion Criteria:

• Prior taxane-containing treatment within 6 months prior to enrollment.
• Prior treatment including chemotherapy and/or endocrine therapy discontinued < 21 days prior to enrollment.
• More than one prior systemic chemotherapy for locally recurrent or metastatic breast cancer.
• Current or prior history of central nervous system metastases.
• History of arterial or venous thrombosis within 1 year prior to enrollment.
• History of bleeding diathesis or bleeding within 14 days prior to enrollment.
• Radiation therapy to a significant portion of bone marrow or prior history of high-dose chemotherapy requiring bone marrow or stem cell support.
• Hypersensitivity to paclitaxel, docetaxel, or drugs using the vehicle cremophor.
• Prior VEGFr targeted therapies within 30 days of enrollment.
• Any anticoagulant therapy within 7 days prior to enrollment, except for warfarin of less than 2mg per day.
• Clinically significant cardiac disease including myocardial infarction or other cardiovascular related event within 1 year before enrollment.
• Uncontrolled hypertension (systolic >150 mmHg; diastolic > 90 mmHg).
• Known HIV positive, hepatitis C positive or hepatitis B surface antigen positive.
• Prior bevacizumab or trastuzumab therapy within 12 weeks of enrollment.
• Non-healing wound, ulcer or fracture.
• Known history of prior episodes of cholecystitis, prior biliary procedure or prior or ongoing biliary disease.
• Unable to take oral medications.
• Not recovered from previous therapies.
• Major surgery within 28 days prior to enrollment.
• Prior malignancy unless treated with curative intent and without evidence of disease for greater than 3 years before enrollment.
• Peripheral neuropathy grade > 1 per CTCAE version 3.0