Trial of Chemotherapy and Avastin as Treatment for Women With Breast Cancer at High Risk for Relapse

Inclusion Criteria:

General health

* Women Age \>18.
* ECOG Performance status 0-1
* Life expectancy must be 3 months. Clinical stage
* Histologically or cytologically adenocarcinoma of breast
* Pre-operative stage II-III per AJCC 6th edition, based on baseline evaluation by clinical examination, breast imaging, and/or preoperative work-up.
* Evidence of residual invasive breast cancer or node positive disease following neoadjuvant chemotherapy.

Prior Therapy

* Patients must have received primary (neoadjuvant) chemotherapy for local or locoregional breast cancer containing an anthracycline and a taxane.
* Patients must have completed definitive resection of primary tumor with adequate excision of gross disease.
* Patients must have residual invasive carcinoma in the breast and/or residual carcinoma in one or more regional nodes following preoperative chemotherapy.

Adequate hematologic and metabolic parameters within four weeks of study entry defined as:

* Absolute neutrophil count ≥1,500/mm3 Platelets ≥ 150,000/mm3
* Total bilirubin ≤ 2.0 mg/dL
* Serum creatinine ≤ 2x upper limit of normal
* Serum calcium ≤1.5x upper normal limit Concurrent treatments
* Current use of anti-coagulants is allowed as long as patients have been on a stable dose for more than 2 weeks with stable INR.
* Chronic therapy with full dose aspirin up to 325 mg/day or standard non-steroidal anti-inflammatory agents is allowed.

Informed consent

* Provision of signed informed consent.

Exclusion Criteria:

Prior therapy

* No prior gemcitabine, continuous infusion 5-FU, or oral fluoropyrimidine (capecitabine, UFT, S-1, 5-FU/eniluracil, etc.)
* No known hypersensitivity to capecitabine or prior unanticipated severe reaction to (capecitabine, UFT, S-1, 5-FU/eniluracil, etc.) therapy or known hypersensitivity to 5-fluorouracil.
* No concurrent or prior endocrine therapy as adjuvant treatment.
* No prior breast radiation
* Current, recent (within 4 weeks of the first infusion of this study), or planned participation in another experimental drug study
* Stage IV breast cancer
* Patients must not have evidence of metastatic disease at enrollment. Women of child-bearing potential.
* Nonpregnant and nonlactating.
* Women of child-bearing potential must have a negative serum pregnancy test and must agree to an effective means of contraception during the entire study period.

Concurrent medical conditions:

* No other active cancers, except non-melanoma skin cancers.
* No serious infection or other serious underlying medical condition that would otherwise impair their ability to receive protocol treatment.
* Patients with clinically significant medical or psychiatric problems which may interfere with treatment on study.

Avastin-specific exclusions:

* Inadequately controlled hypertension (defined as systolic blood pressure 150 and/or diastolic blood pressure \> 100 mmHg on antihypertensive medications)
* Any prior history of hypertensive crisis or hypertensive encephalopathy
* New York Heart Association (NYHA) Grade II or greater congestive heart failure
* Known CNS disease
* Significant vascular disease (e.g., aortic aneurysm, aortic dissection)
* 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 a 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, ulcer, or bone fracture
* Proteinuria at screening as demonstrated by urine dipstick for proteinuria ≥ 2+ (patients discovered to have ≥2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour
* urine collection and must demonstrate ≤ 1g of protein in 24 hours to be eligible).
* Known hypersensitivity to any component of bevacizumab any history of stroke or transient ischemic attack at any time
* History of myocardial infarction or unstable angina within 12 months of study enrollment Inability to comply with study and/or follow-up procedures