The purpose of this research study is to determine the effects of the combination of bevacizumab, vinorelbine, and trastuzumab on participants and their cancer.

• Participants will receive bevacizumab intravenously every 2 weeks. They will also receive trastuzumab and vinorelbine intravenously once a week. Therefore, treatments will alternate between receiving all three drugs (1st week, third week, fifth week, etc.) and receiving only trastuzumab and vinorelbine (2nd week, fourth week, sixth week, etc.) A treatment cycle lasts four weeks.
• During all treatment cycles a physical exam will be performed and the participant will be asked general health and specific questions about any problems they are experiencing.
• X-ray, CT scans, and/or MRI scans will be performed every 8 weeks (every 2 cycles) in order to assess the effect of the study treatment on the participants cancer. These tests are considered standard of care in patients receiving chemotherapy.
• Once a week blood counts will be performed and at least every 4 weeks, chemistry and other tests to measure any additional effect of the study drug and disease status will be checked. These tests are also considered standard of care for patients receiving chemotherapy.
• At the beginning of the study and at the 4- and 8-week time point, additional blood will be drawn in order to conduct research blood tests to measure the presence of cancer cells in the blood.
• A urine test and MUGA scan or echocardiogram will be done every 8 weeks while the participant in on the study.
• Participants can remain on the research study as long as the study treatment appears to be working and they are not experiencing unacceptable side effects.

Inclusion Criteria:

• Histologically or cytologically confirmed invasive breast cancer, with metastatic disease.
• HER2-positive tumor
• Measurable disease defined as at least one lesion that can be accurately measured in at least one dimension as 20mm or greater with conventional techniques or as 10mm or greater with spiral CT scan
• 18 years of age or older
• Life expectancy of more than 12 weeks
• ECOG Performance Status of 0 or 1
• Normal organ and marrow function as outlined in the protocol
• Left ventricular ejection fraction 50% or greater as determined by RVG or echocardiogram within 30 days prior to initiation of protocol therapy
• Patients with stable or previously treated CNS metastases are eligible for study participation, provided there is no history of clinically significant CNS bleeding
• Men and women of child-bearing potential must agree to use adequate contraception prior to study entry and for the duration of study participation

COHORT A:

• No prior chemotherapy for treatment of metastatic breast cancer
• May NOT have received prior treatment with trastuzumab for recurrent or metastatic breast cancer
• No prior vinorelbine for treatment of breast cancer
• No prior bevacizumab for treatment of breast cancer
• May have received prior radiation therapy and/or any number of lines of hormonal therapy
• Prior trastuzumab therapy in the adjuvant setting is also allowed, providing that relapse occured at least 12 months following the last dose
• Must have recovered from all reversible toxicities related to prior therapy and may not have any pre-existing treatment-related toxicities in excess of Grade 1. Patients must have stopped prior radiation therapy at least 7 days prior to beginning protocol treatment

COHORT B:

• One prior line of chemotherapy for treatment of metastatic breast cancer or recurrence of breast cancer within 12 months of completion of adjuvant trastuzumab
• No prior vinorelbine for treatment of breast cancer
• No prior bevacizumab for treatment of breast cancer
• May have received prior radiation therapy and/or any number of lines of hormonal therapy
• Must have recovered from all reversible toxicities related to prior therapy and may not have any pre-existing treatment-related toxicities in excess of Grade 1. Patients must have stopped prior radiation therapy at least 7 days prior to beginning protocol treatment

Exclusion Criteria:

• Patients who have had chemotherapy within 14 days prior to entering the study, ot those who have not recovered adequately from adverse events due to agents administered earlier
• Concurrent radiation therapy
• History of Grade 3 or 4 allergic reactions attributed to compounds of similar chemical or biologic composition as the agents used in this study
• Prior therapy with bevacizumab or vinorelbine
• Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored bevacizumab cancer study
• Inadequately controlled hypertension
• Prior history of hypertensive crisis of hypertensive encephalopathy
• NHYA Grade II or greater congestive heart failure
• History of myocardial infarction of unstable angina within 6 months prior to study enrollment
• History of stroke or transient ischemic attack within 6 months prior to study enrollment
• Progressive or untreated CNS metastases
• Significant vascular disease within 6 months prior to study enrollment
• Symptomatic peripheral vascular disease
• Evidence of bleeding diathesis or coagulopathy
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study
• Core biopsy or other minor surgical procedure, excluding placement of vascular access device, within 7 days prior to study enrollment
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment
• Serious non-healing wound, active ulcer, or untreated bone fracture
• Proteinuria at screening
• Pregnant or lactating
• Current and ongoing treatment with full-dose warfarin or its equivalent