• PFS in individual primary chemotherapy cohorts [ Time Frame: Length of study ] [ Designated as safety issue: No ]
• 1-year survival; overall survival [ Time Frame: 1-year; until death or loss to follow up ] [ Designated as safety issue: No ]
• Objective response and duration of objective response [ Time Frame: Length of study ] [ Designated as safety issue: No ]
• Serious and selected adverse events [ Time Frame: Length of study ] [ Designated as safety issue: No ]

This Phase III, multicenter, randomized, placebo-controlled, blinded trial is designed to evaluate the efficacy and safety of bevacizumab when combined with standard chemotherapy compared with chemotherapy alone in subjects with previously treated MBC.

• Drug: bevacizumab
• Drug: chemotherapy
• Drug: placebo

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 [U.S. 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
• 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 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 ER and PR status
• Radiation therapy other than for palliation or brain metastasis, biologic therapy, or chemotherapy for MBC within 21 days prior to Day 0
• Prior therapy with bevacizumab or other VEGF pathway-targeted therapy
• Untreated brain metastasis
• Inadequately controlled hypertension
• Unstable angina
• New York Heart Association Grade II or greater 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