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.