AZD2171 and Combination Chemotherapy in Treating Women With Locally Advanced Breast Cancer

OBJECTIVES: Primary * Determine the overall pathologic complete response rate in women with previously untreated, locally advanced breast cancer treated with neoadjuvant AZD2171, doxorubicin hydrochloride, cyclophosphamide, and docetaxel. Secondary * Compare changes in pretreatment levels of pKDR after 1 course of AZD2171 vs no medication. * Determine the number of patients who respond to combination therapy beginning with the second course of therapy. * Determine the clinical response rate in patients treated with this regimen. * Determine the safety of this regimen in these patients. * Determine the changes in tumor proliferation (Ki67) in these patients. * Determine the pharmacokinetics and pharmacogenetics of this regimen in these patients. * Correlate angiogenic parameters with tumor response in these patients. * Determine tumor vascularity and permeability before and after treatment as seen on dynamic contrast-enhanced MRI and initial area under the gadolinium curve. * Determine tumor choline levels before and after treatment as measured by quantitative single-voxel MR spectroscopy and correlate with response. OUTLINE: This is a multicenter, randomized, pilot study. Patients are randomized to 1 of 2 treatment arms. * Arm I: Patients receive oral AZD2171 once daily on days 1-7\* during course 1. During the second and subsequent courses, patients receive oral AZD2171 once daily on days 1-21, doxorubicin hydrochloride IV over 3-5 minutes, cyclophosphamide IV over 30 minutes, and docetaxel IV over 1 hour on day 1. Patients also receive filgrastim (G-CSF) subcutaneously (SC) on days 2-11 or pegfilgrastim SC on day 2. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. NOTE: \*If biopsy cannot be scheduled prior to day 7 or 8 of course 1, AZD2171 alone can be continued for up to 14 days. * Arm II (control): Beginning during the second course, patients receive AZD2171, doxorubicin hydrochloride, cyclophosphamide, docetaxel, and G-CSF or pegfilgrastim as in arm I. All patients undergo tumor biopsiesat at baseline, before courses 2 and 4, and 3 weels after completion of study treatment. Tissue is examined for various biomarkers (phosphorylated-KDR, -MAPK, and -Akt, Ki67, VEGF, and p53) and for DNA ploidy analysis\*\*. NOTE: \*\*Patients also undergo dynamic contrast-enhanced MRI and quantitative magnetic resonance spectroscopy 1 week before beginning therapy, 24 hours after starting therapy, prior to courses 2, 4, and 6, and 3 weeks after completion of study treatment. After completion of AZD2171 and chemotherapy, patients undergo surgical resection. After completion of study treatment, patients are followed for 4 weeks. PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.