RATIONALE: Bevacizumab may stop the growth of tumor cells by stopping blood flow to the tumor. Drugs used in chemotherapy such as docetaxel and doxorubicin use different ways to stop tumor cells from dividing so they stop growing or die. Combining bevacizumab with docetaxel and doxorubicin may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining bevacizumab with docetaxel and doxorubicin in treating patients who have inflammatory or locally advanced stage IIB or stage III breast cancer that has not been previously treated with chemotherapy and/or radiation therapy.

OBJECTIVES:

• Determine the effect of bevacizumab on angiogenic parameters, primary molecular parameters (endothelial apoptosis, endothelial proliferation, or tissue vascular endothelial growth factor), and dynamic MRI parameters in patients with previously untreated inflammatory or locally advanced breast cancer also treated with doxorubicin and docetaxel.
• Determine the variability of primary molecular parameter values in patients treated with this regimen.
• Correlate the primary parameters with clinical results and time to disease progression or recurrence in patients treated with this regimen.
• Determine whether bevacizumab is associated with the production of a prothrombotic state in these patients.

OUTLINE: Patients receive bevacizumab IV over 30-90 minutes on day 1 of courses 1-7. Patients also receive doxorubicin IV and docetaxel IV over 1 hour on day 1 and filgrastim (G-CSF) subcutaneously (SC) on days 2-11 or pegfilgrastim SC on day 2 of courses 2-7. Treatment repeats every 3 weeks for 7 courses in the absence of disease progression or unacceptable toxicity.

After completion of course 7, patients undergo reassessment of need for surgery.

After completion of any surgery, patients receive bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for 8 courses in the absence of disease progression or unacceptable toxicity. Patients who are estrogen receptor and/or progesterone receptor positive may receive oral tamoxifen or anastrozole daily for 5 years beginning with course 8 of bevacizumab.

Patients are followed every 3 months for 1 year and then every 3-6 months for 2 years.

PROJECTED ACCRUAL: A total of 23 patients will be accrued for this study within 1 year.

• Biological: bevacizumab
• Biological: filgrastim
• Biological: pegfilgrastim
• Drug: docetaxel
• Drug: doxorubicin hydrochloride
• Procedure: conventional surgery

• Thukral A, Thomasson DM, Chow CK, Eulate R, Wedam SB, Gupta SN, Wise BJ, Steinberg SM, Liewehr DJ, Choyke PL, Swain SM. Inflammatory breast cancer: dynamic contrast-enhanced MR in patients receiving bevacizumab--initial experience. Radiology. 2007 Sep;244(3):727-35.
• Wedam SB, Low JA, Yang SX, Chow CK, Choyke P, Danforth D, Hewitt SM, Berman A, Steinberg SM, Liewehr DJ, Plehn J, Doshi A, Thomasson D, McCarthy N, Koeppen H, Sherman M, Zujewski J, Camphausen K, Chen H, Swain SM. Antiangiogenic and antitumor effects of bevacizumab in patients with inflammatory and locally advanced breast cancer. J Clin Oncol. 2006 Feb 10;24(5):769-77. Epub 2006 Jan 3.

DISEASE CHARACTERISTICS:

• Histologically confirmed inflammatory or locally advanced stage IIB, IIIA, IIIB, or IIIC breast cancer

  • Previously untreated with chemotherapy and/or radiotherapy
• No carcinomatous meningitis, brain metastases, or primary brain tumor

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Sex:

• Male or female

Menopausal status:

• Not specified

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• No prior bleeding diathesis or coagulopathy

Hepatic:

• Bilirubin no greater than upper limit of normal (ULN) (2 times ULN if Gilbert's disease is present and elevation is not related to tumor or other liver diseases)
• AST/ALT no greater than 1.5 times ULN
• Alkaline phosphatase no greater than 2.5 times ULN
• INR no greater than 1.50

Renal:

• Creatinine no greater than 1.5 mg/dL
• 24-hour urine protein less than 500 mg
• No prior primary renal disease except infection

Cardiovascular:

• LVEF at least 50%
• No New York Heart Association class II-IV congestive heart failure
• No serious cardiac arrhythmia requiring medication
• No grade II or greater peripheral vascular disease within the past 12 months
• No symptoms or signs of clinical heart failure

• No uncontrolled hypertension

  • Systolic blood pressure greater than 160 mm Hg OR
  • Diastolic blood pressure greater than 100 mm Hg
• No prior deep venous thrombosis
• No arterial thromboembolic event (e.g., transient ischemic attack, cerebrobascular accident, unstable angina, or myocardial infarction) within the past 6 months
• No history of stroke
• No clinically significant peripheral artery disease
• No other clinically significant cardiovascular disease

Pulmonary:

• No pulmonary embolism

Neurologic:

• See Disease Characteristics
• No uncontrolled seizures
• No clinical neuropathy grade 2 or greater
• No other CNS disease

Other:

• No active infection requiring IV antibiotics
• No nonhealing wound or bone fracture within the past 28 days
• No gastrointestinal bleeding within the past 6 months
• No other malignancy within the past 5 years except carcinoma in situ of the cervix or nonmelanoma skin cancer
• No hypersensitivity to products containing polysorbate 80 (Tween 80)
• No known hypersensitivity to E. coli-derived products
• No other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that would preclude study entry
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective nonhormonal contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• See Disease Characteristics

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics

Surgery:

• More than 28 days since prior major surgery

Other:

• At least 10 days since prior full-dose oral or parenteral anticoagulants or chronic aspirin (greater than 325 mg/day)
• No other concurrent antitumor therapy
• No other concurrent investigational drugs