Statement: bothered by question is a question about whether an individual is bothered by something. only patients with a HER2-positive status can take part in the primary trial.
Primary_evidence: 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.