RATIONALE: Drugs used in chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some find tumor cells and help kill them or carry tumor-killing substances to them. Others interfere with the ability of tumor cells to grow and spread. Bevacizumab may also stop the growth of breast cancer by blocking blood flow to the tumor. Giving combination chemotherapy together with bevacizumab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving bevacizumab after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase II trial is studying the side effects and how well giving paclitaxel albumin-stabilized nanoparticle formulation and carboplatin together with bevacizumab works in treating women undergoing surgery for stage II or stage III breast cancer.

OBJECTIVES:

Primary

• To determine the complete pathological response (pCR) in the breast/axillary lymph nodes in women with stage II or III breast cancer treated with neoadjuvant therapy comprising paclitaxel albumin-stabilized nanoparticle formulation, carboplatin, and bevacizumab followed by surgery and adjuvant bevacizumab.
• To determine the side effects of this regimen in these patients.

Secondary

• To evaluate dynamic contrast-enhanced magnetic resonance imaging in assessing pCR.
• To measure LZTS1 gene expression before and after neoadjuvant therapy to evaluate whether LZTS1 gene expression correlates with pCR.
• To evaluate the feasibility and toxicity of adjuvant bevacizumab when administered for 6 months.

OUTLINE:

• Neoadjuvant therapy: Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes and carboplatin IV over 30 minutes on days 1, 8, and 15 and bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for 5 courses. After completion of course 5, patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes and carboplatin IV over 30 minutes on days 1, 8, and 15. Patients then proceed to surgery.
• Surgery: Approximately 4-5 weeks after completion of neoadjuvant therapy, patients undergo definitive surgery (either lumpectomy or mastectomy). Patients with node-positive disease or inflammatory breast cancer at baseline also undergo axillary lymph node dissection. Patients then proceed to adjuvant therapy.
• Adjuvant therapy: Beginning approximately 6 weeks after surgery, patients receive bevacizumab IV over 30-90 minutes once every 3 weeks for 6 months. Patients with hormone receptor-positive disease also receive endocrine therapy. Patients may also receive additional adjuvant chemotherapy or radiotherapy at the discretion of the treating physician.

Patients undergo dynamic contrast-enhanced magnetic resonance imaging at baseline, after course 2 of neoadjuvant therapy, and after completion of neoadjuvant therapy (prior to definitive surgery) for assessment of tumor response. Tumor tissue is collected at baseline and during surgery for correlative laboratory studies. LZST1 gene expression is assessed by immunohistochemistry before and after neoadjuvant therapy.

Inclusion:

• Histologically confirmed breast cancer
• Clinically or radiographically measurable residual tumor after core biopsy
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Age ≥18 yrs
• Absolute neutrophil count ≥ 1,500/mm³
• Hemoglobin ≥ 9 g/dL
• Platelet count ≥ 100,000/ mm³
• Creatinine ≤ 1.5 times upper limit of normal (ULN)
• Urine protein:creatinine ratio < 1.0
• AST (aspartate aminotransferase) and ALT ≤ 2.5 times ULN
• Alkaline phosphatase ≤ 2.5 times ULN
• Bilirubin normal
• Women of childbearing potential must use effective contraception
• Left ventricular ejection fraction (LVEF) normal by echocardiogram or MUGA

Exclusion:

• No residual tumor after initial biopsy
• Peripheral neuropathy of grade 2 or higher
• HER-2 neu overexpression either by IHC 3+ or FISH+
• No history of any prior treatment of breast cancer.
• No history of unstable angina or myocardial infarction within the past 12 months
• Pregnant or nursing women
• Anticoagulation therapy within the last 6 months
• History of gastrointestinal bleeding
• Recent hemoptysis
• No known hepatitis B or HIV seropositivity
• No inadequately controlled hypertension, defined as systolic blood pressure (BP) > 150 mm Hg and/or diastolic BP > 100 mm Hg despite antihypertensive medications
• History of hypertensive crisis or hypertensive encephalopathy
• New York Heart Association class II-IV congestive heart failure
• History of stroke or transient ischemic attack at any time
• Significant vascular disease (e.g., aortic aneurysm or aortic dissection)
• No symptomatic peripheral vascular disease
• Evidence of bleeding diathesis or coagulopathy
• Significant traumatic injury within the past 28 days
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
• Serious, non-healing wound, ulcer, or bone fracture
• Known hypersensitivity to any component of bevacizumab