RATIONALE: Drugs used in chemotherapy, such as carboplatin and paclitaxel albumin-stabilized nanoparticle formulation, 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 block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry cancer-killing substances to them. Bevacizumab may also stop the growth of breast cancer by blocking blood flow to the tumor. Giving carboplatin and paclitaxel together with bevacizumab may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving carboplatin and paclitaxel together with bevacizumab works in treating patients with locally recurrent or metastatic breast cancer.

OBJECTIVES:

Primary

• To determine the progression-free survival of patients with locally recurrent or metastatic breast cancer treated with carboplatin, paclitaxel albumin-stabilized nanoparticle formulation, and bevacizumab as first-line therapy.

Secondary

• To determine the response rate in these patients.
• To determine the overall survival of these patients.
• To evaluate the toxicity profile of this regimen in these patients.

OUTLINE: Patients receive carboplatin IV over 1 hour and bevacizumab IV on days 1, 22 and 43. Patients also receive paclitaxel albumin-bound nanoparticle formulation IV over 30 minutes on days 1, 8 ,15, 22, 29, 36, 43, and 50. Treatment continues in the absence of disease progression or unacceptable toxicity.

Formalin-fixed paraffin-embedded archived tumor tissue samples are assessed by immunohistochemistry (IHC) for various biomarkers. Levels of Notch-1, Notch-4, cyclin A, cyclin B, Jagged-1, and DLL4 in tumor-associated endothelial cells are correlated with response in both estrogen- and progesterone-positive and negative tumors, and independently of p53 status.

After completion of study treatment, patients are followed for up to 2 years.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed primary adenocarcinoma of the breast

  • Locally recurrent or metastatic disease

• Must have HER-2-negative breast cancer or, if HER-2-positive, must be unable to receive trastuzumab (Herceptin®) or have previously received trastuzumab in the past

• Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm by conventional techniques or as > 10 mm by spiral CT scan.

• No known CNS disease

• Hormone receptor status not specified

PATIENT CHARACTERISTICS:

Inclusion criteria:

• Postmenopausal status not specified
• ECOG performance status (PS) 0-1 OR Karnofsky PS 70-100%
• Life expectancy > 12 weeks
• WBC ≥ 3,000/mcL
• Absolute neutrophil count ≥ 1,500/mcL
• Platelet count ≥ 100,000/mcL
• Total bilirubin normal
• AST and ALT ≤ 2.5 times upper limit of normal (ULN)
• Alkaline phosphatase ≤ 2.5 times ULN (unless bone metastasis is present in the absence of liver metastasis)
• Creatinine ≤ 1.5 mg/dL
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other concurrent malignancies within the past 5 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

Exclusion criteria:

• Pre-existing neuropathy ≥ grade 1

• Uncontrolled intercurrent illness including, but not limited to, any of the following:

  • Ongoing or active infection
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Serious, non-healing wound, ulcer, or bone fracture
  • Psychiatric illness/social situations that would limit compliance with study requirements

• Inadequately controlled hypertension (defined as systolic blood pressure > 150 mm Hg and/or diastolic blood pressure > 100 mm Hg on antihypertensive medications)

• History of hypertensive crisis or hypertensive encephalopathy

• New York Heart Association class II-IV congestive heart failure

• History of myocardial infarction or unstable angina within the past 6 months

• History of stroke or transient ischemic attack within the past 6 months

• Significant vascular disease (e.g., aortic aneurysm, aortic dissection)

• 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

• Proteinuria, as demonstrated by either urine protein:creatinine ratio ≥ 1.0 OR urine dipstick for proteinuria ≥ 2+

  • Patients discovered to have ≥ 2+ proteinuria on dipstick urinalysis at baseline must demonstrate 24-hour urine protein ≤ 1g

• History of allergy or hypersensitivity to paclitaxel albumin-stabilized nanoparticle formulation, paclitaxel, bevacizumab, carboplatin, albumin, drug product excipients, or chemically similar agents

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• Recovered from all prior therapy

• No prior chemotherapy for locally recurrent or metastatic disease

• Prior neoadjuvant or adjuvant chemotherapy allowed

• More than 1 week since prior core biopsy or other minor surgical procedure, excluding placement of a vascular access device

• More than 4 weeks since prior and no concurrent major surgical procedure or open biopsy

• More than 4 weeks since prior radiotherapy

• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)

• At least 1 year since prior taxane regimen

• No other concurrent investigational agents

• Concurrent anticoagulation allowed, provided the following criteria are met:

  • Stable dose of warfarin or low molecular weight heparin
  • INR within desired range (2-3)
  • No evidence of active bleeding or coagulopathy

• No concurrent combination antiretroviral therapy for HIV-positive patients

• No other concurrent radiotherapy, chemotherapy, immunotherapy, or antitumor hormonal therapy