The purpose of this research study is to study the effects (good and bad) of bevacizumab alone, bevacizumab with low-dose continuous chemotherapy (called metronomic chemotherapy), or bevacizumab with capecitabine, on you and your cancer. The goals of the study will be to:

• Examine the safety of these drugs
• See how easy or difficult it is to be treated with them
• Monitor for any signs of recurrent cancer
• Look at blood markers that might indicate how the treatment is working

This study is broken into 4 groups (A, B, C, and D). Enrollment closed to all groups in May 2008.

The first forty subjects (Group A) in this study were treated with Bevacizumab only, which is given through a vein over 1-2 hours every 3 weeks, for a total of approximately 12 months (17 cycles). Each cycle consists of 3 weeks.

The next forty subjects (Group B) were treated with Bevacizumab and metronomic CM chemotherapy. These subjects took cyclophosphamide (1 pill by mouth every day), methotrexate, (1 pill taken by mouth twice a day for the first two days of each week) and Bevacizumab (once every 3 weeks). The treatments with cyclophosphamide, methotrexate and Bevacizumab will continue for approximately 6 months (8 cycles). Then for the next 6 months, they received Bevacizumab treatments only. The total time on this study will be about 12 months (17 cycles).

The next forty subjects (Group C) were treated with Bevacizumab and Capecitabine chemotherapy. These subjects took Capecitabine pills twice a day for 14 days, then one week of rest, to complete a 21-day cycle. There will be a total of 6 cycles of Capecitabine, meaning 18 weeks of treatment with both Capecitabine and Bevacizumab. Then received Bevacizumab treatments only (11 cycles) to complete 12 months of therapy. Total duration of your treatment will be about 12 months or 17 cycles of therapy.

The last forty subjects (Group D) are being treated with Bevacizumab and Capecitabine chemotherapy on a different schedule. These subjects will take Capecitabine pills twice a day for 7 days, then one week of rest and repeat this for a total of 24 weeks (6 cycles). Each cycle will last for 4 weeks (28 days). There will be a total of 6 cycles of Capecitabine, meaning 24 weeks of treatment with both Capecitabine and Bevacizumab. Bevacizumab will be given every two weeks for a total of 24 weeks (6 cycles). Then they will receive Bevacizumab treatments only, every 3 weeks for additional 27 weeks (9 cycles) to complete 12 months of therapy. For the last 9 cycles of Bevacizumab therapy each cycle will consist of 3 weeks. Total duration of treatment will be about 12 months or 15 cycles of therapy.

Inclusion Criteria:

• Histologically or cytologically confirmed invasive breast cancer, preoperative stages II-III per AJCC 6th edition, based on baseline evaluation by clinical examination and/or breast imaging
• Patients must have completed preoperative (neoadjuvant) chemotherapy with a standard chemotherapy regimen. No more chemotherapy should be planned.
• Patients must have completed definitive resection of primary tumor with adequate excision of gross disease.
• For patients receiving adjuvant radiation therapy, treatment must be completed prior to initiation of protocol therapy.
• Patients must have the presence of significant residual invasive disease on pathologic review following their preoperative chemotherapy.
• LVEF > institutional limits of normal after preoperative chemotherapy, as assessed by ECHO or nuclear medicine gated study, within 30 days prior to initiating protocol-based treatment.
• ECOG performance status 0-1

Exclusion Criteria:

• Inadequate organ function, as measured by laboratory assessment after preoperative chemotherapy and within 14 days of beginning protocol-based treatment
• Patients with metastatic disease are ineligible.
• Known HIV infection
• Patients may not be pregnant, expect to become pregnant, plan to conceive a child while on study, or breastfeeding
• Uncontrolled intercurrent illness
• Non-healing wounds or major surgical procedures (such as breast surgery) other than that for venous access device or diagnostic study are not permitted within 28 day prior to enrollment
• History of abdominal fistula, GI perforation, intra-abdominal abscess, or serious, non-healing wound, ulcer, or bone fracture within 6 months prior to initiating bevacizumab
• Patients with any history of arterial thromboembolic events, including transient ischemic attack (TIA), cerebrovascular event (CVA), unstable angina, or myocardial infarction (MI) within the past 6 months. Patients with clinically significant peripheral arterial disease should also be excluded
• History of bleeding diathesis or coagulopathy
• History of grade 3 or 4 allergic reactions to compounds of similar chemical or biologic composition to cyclophosphamide (such as other alkylating agents) or methotrexate (such as other antimetabolites)
• Prior history of malignancy treated without curative intent, excluding nonmelanomatous skin cancer
• Patients with large or rapidly accumulating pleural or abdominal effusions
• Current use of anticoagulants is allowed as long as patients have been on a stable dose for more than two weeks with stable INR
• Chronic therapy with full dose aspirin (< 325 mg/day) or standard non-steroidal anti-inflammatory agents is allowed
• Patients may not receive other investigational agents while on study