A Study to Evaluate the Safety and Efficacy of Bevacizumab in Combination With Chemotherapy in Previously Treated Metastatic Breast Cancer (RIBBON 2)

Inclusion Criteria:

* Signed informed consent form.
* ≥ 18 years of age.
* Histologically confirmed carcinoma of the breast with measurable or non-measurable metastatic disease that has progressed (patients with a history of brain metastasis are eligible for study participation \[USA only\], as long as their brain metastases have been treated and they have no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone).
* Progression of disease during or following administration of one (non-investigational) chemotherapy regimen administered in the first-line setting.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* For women of childbearing potential, use of an effective means of non-hormonal contraception.
* Life expectancy ≥ 3 months.
* Willingness and capacity to comply with study and follow-up procedures.

Exclusion Criteria:

* Prior hormonal therapy only as treatment for metastatic disease without chemotherapy. Patients must have received chemotherapy for their metastatic disease in the first-line setting. Hormone therapy alone is not allowed.
* For subjects who have received prior anthracycline-based therapy, documentation of left ventricular ejection fraction \< 50% by either multiple gated acquisition (MUGA) or echocardiogram (ECHO).
* Treatment with more than one prior cytotoxic regimen for metastatic breast cancer (MBC).
* HER2-positive status (patients who have unknown HER2 status, and for whom determination of HER2 status is not possible, are eligible for this study).
* Unknown estrogen receptor (ER) and progesterone receptor (PR) status.
* Radiation therapy other than for palliation or brain metastasis, biologic therapy, or chemotherapy for MBC within 21 days prior to Day 0 (Day 1 of Cycle 1 of treatment).
* Prior therapy with bevacizumab or other vascular endothelial growth factor (VEGF) pathway-targeted therapy.
* Untreated brain metastasis.
* Inadequately controlled hypertension.
* Unstable angina.
* New York Heart Association Grade II or greater congestive heart failure (CHF).
* History of myocardial infarction within 6 months prior to Day 0 (the day of the first bevacizumab/placebo infusion).
* History of stroke or transient ischemic attack within 6 months prior to Day 0.
* Clinically significant peripheral vascular disease.
* Evidence of bleeding diathesis or coagulopathy.
* Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0; anticipation of need for major elective surgical procedure during the study.
* Minor surgical procedures, fine-needle aspirations, or core biopsies within 7 days prior to Day 0.
* History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 0.
* Serious, non-healing wound, ulcer, or bone fracture.
* History of anaphylactic reaction to monoclonal antibody therapy not controlled with treatment premedication.
* History of other malignancies within 5 years of Day 0, except for tumors with a negligible risk for metastasis or death, such as adequately controlled basal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
* inadequate organ function.
* Pregnancy (positive serum pregnancy test) or lactation.
* Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the subject at high risk from treatment complications.