RATIONALE: Drugs used in chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation, doxorubicin, and cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Colony-stimulating factors, such as pegfilgrastim, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some find tumor cells and kill them or carry tumor-killing substances to them. Others interfere with the ability of tumor cells to grow and spread. Bevacizumab may also may stop the growth of tumor cells by blocking blood flow to the tumor. Giving these treatments before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. It is not yet known which treatment regimen is more effective in treating women with breast cancer.

PURPOSE: This randomized phase II trial is studying paclitaxel albumin-stabilized nanoparticle formulation, doxorubicin, cyclophosphamide, and pegfilgrastim to compare how well they work when given with or without bevacizumab in treating women with inflammatory or locally advanced breast cancer.

OBJECTIVES:

• To compare the pathologic complete response rates in women with HER2/neu-negative inflammatory or locally advanced breast cancer treated with paclitaxel albumin-stabilized nanoparticle formulation, doxorubicin hydrochloride, cyclophosphamide, and pegfilgrastim with vs without bevacizumab.
• To compare the overall survival of patients treated with these regimens.
• To assess whether there is a correlation between bevacizumab and stratification factors (type of disease and hormone receptor status).
• To compare the toxicities of these regimens.
• To explore the molecular biomarkers related to the biology and outcome of inflammatory breast cancer.
• To explore potential molecular biomarkers that predict response to therapy and drug sensitivity.
• To evaluate biomarkers with respect to the sequence of paclitaxel albumin-stabilized nanoparticle formulation and doxorubicin hydrochloride/cyclophosphamide/pegfilgrastim administration in patients not receiving bevacizumab.
• To explore residual cancer burden and correlate it with outcome.
• To evaluate the time to treatment failure prior to surgery.
• To evaluate disease-free survival from the time of surgery in patients undergoing definitive surgery.

OUTLINE: This is a multicenter study. Patients are stratified according to type of disease (inflammatory vs locally advanced breast cancer) and hormone receptor status (positive [estrogen receptor (ER)+ and/or progesterone receptor (PgR)+] vs negative [ER- and PgR-]). Patients are randomized to 1 of 3 treatment arms.

• Arm I: Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on day 1 and bevacizumab IV over 30- to 90-minutes on day 1 of weeks 1-12. Patients then receive doxorubicin hydrochloride IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2 of weeks 14, 16, 18, 20, 22, and 24.
• Arm II: Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on day 1 of weeks 1-12. Patients then receive doxorubicin hydrochloride IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2 of weeks 14, 16, 18, 20, 22, and 24.
• Arm III: Patients receive doxorubicin hydrochloride IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2 of weeks 1, 3, 5, 7, 9, and 11. Patients then receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on day 1 of weeks 14-25.

In all arms, patients with stable or responding disease undergo surgery 3-6 weeks after completion of chemotherapy. Patients may then undergo radiotherapy 5 days a week for 6 weeks.

Serum, whole blood, and tissue samples are collected periodically for biomarker analysis, circulating endothelial cell analysis, and pharmacogenomic studies, respectively.

After completion of study treatment, patients are followed every 6 months for 1 year and then annually for 4 years.

DISEASE CHARACTERISTICS:

• Histologically or pathologically confirmed breast cancer meeting one of the following criteria:

  • Locally advanced disease (stage IIIB disease, stage IIB/IIIA, or stage IIIC disease)

  • Inflammatory disease meeting the following two clinicopathologic criteria:

    • Diffuse erythema AND edema (peau d'orange) of the breast involving the majority of the skin of the breast, i.e., more than 50%
    • A biopsy demonstrating cancer either within the dermal lymphatics OR in the breast parenchyma itself

• HER2/neu-negative tumor as demonstrated by 0 or 1+ (weak or no staining) by DAKO, IHC, or equivalent test OR no gene amplification by FISH*

  • 2+ by DAKO or IHC allowed provided FISH* negative

• NOTE: *A negative FISH test ratio is < 1.8 or FISH HER2 gene copy < 4.0; if only a positive or negative result is available from the FISH test, a negative result is acceptable for study entry

• Hormone receptor status known

PATIENT CHARACTERISTICS:

• Menopausal status not specified

• Zubrod performance status 0-2

• Granulocyte count > 1,500/mm^3

• ANC ≥ 1,500/mm^3

• Platelet count > 100,000/mm^3

• Hemoglobin 9.0 g/dL

• Serum creatinine ≤ 1.5 times upper limit of normal (ULN)

• Bilirubin ≤ 1.5 mg/dL

• ALT and AST ≤ 3 times ULN

• Alkaline phosphatase ≤ 2.5 ULN (unless bone metastasis is present in the absence of liver metastasis)

• Urine protein:creatinine ratio ≤ 0.5 OR urine protein < 1,000 mg on 24-hour urine collection

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• Able to take oral medications (e.g., no uncontrolled nausea, vomiting, or diarrhea, lack of physical integrity of the upper gastrointestinal tract, or malabsorption syndrome)

• QTc < 500 msec by EKG

• LVEF normal by MUGA or ECHO (for patients with hypertension or for patients > 60 years of age)

• NYHA class II cardiac function by baseline ECHO/MUGA (for patients who have received central thoracic radiotherapy that included the heart in the radiotherapy port, or for patients who have a history of class II heart failure but are asymptomatic on treatment are eligible)

• No history of stroke (cerebrovascular accident), transient ischemic attack, or cardiac event within the past 12 months, including any of the following:

  • Myocardial infarction (including severe/unstable angina)
  • Coronary/peripheral artery bypass graft
  • Symptomatic congestive heart failure
  • Pulmonary embolism

• No poorly controlled hypertension, defined as recurrent or persistent (≥ 24 hours) elevated blood pressure (i.e., systolic blood pressure ≥ 140 mm Hg and/or diastolic blood pressure ≥ 90 mm Hg)

• No other malignancy within the past 5 years except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer

• Peripheral neuropathy < grade 2

PRIOR CONCURRENT THERAPY:

• No prior tyrosine kinase inhibitors
• More than 5 years since prior chemotherapy, radiotherapy, or biologic therapy (e.g., trastuzumab or bevacizumab) for invasive breast cancer
• At least 7 days since prior hormonal therapy
• At least 7 days since prior and no concurrent strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole) or grapefruit juice
• No concurrent CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, St. John's wort)
• No other concurrent therapy for the treatment of breast cancer except for bisphosphonates
• No concurrent brachytherapy