A multicenter, placebo-controlled, double-blind randomised phase II trial of neoadjuvant treatment with single-agent bevacizumab or placebo, followed by six cycles of docetaxel, doxorubucin, and cyclophosphamide (TAC), with or without bevacizumab, in patients with stage II or stage III breast cancer.

INTERVENTION: Trade Name: Avastin Product Name: Bevacizumab Product Code: RO4876646 Pharmaceutical Form: Concentrate for solution for infusion INN or Proposed INN: Bevacizumab CAS Number: 216974‐75‐3 Current Sponsor code: RO4876646 Other descriptive name: rhuMAb, VEGF, anti‐VEGF Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 25mg/ml‐ Pharmaceutical form of the placebo: Powder for solution for infusion Route of administration of the placebo: Intravenous use Trade Name: Doxorubicin Product Name: Doxorubicin Pharmaceutical Form: Concentrate for solution for infusion INN or Proposed INN: Doxorubicin Concentration unit: mg/m2 milligram(s)/square meter Concentration type: equal Concentration number: 50‐ Trade Name: Cyclophosphamide Product Name: Cyclophosphamide Pharmaceutical Form: Intravenous infusion INN or Proposed INN: Cyclophosphamide Concentration unit: mg/m2 milligram(s)/square meter Concentration type: equal Concentration number: 500‐ Trade Name: Docetaxel Product Name: Docetaxel Pharmaceutical Form: Intravenous infusion INN or Proposed INN: Docetaxel Concentration unit: mg/m2 milligram(s)/square meter Concentration type: equal Concentration number: 75‐ CONDITION: Stage II or Stage III breast cancer PRIMARY OUTCOME: Main Objective: •To evaluate the safety and toxicity of the TAC regimen with the addition of bevacizumab given as preoperative therapy to patients with Stage II or Stage III breast cancer; •To estimate change from baseline expression of HIF1a as a measure of tumor angiogenesis, after a single dose of bevacizumab as compared to placebo; Primary end point(s): Efficacy Assessments; ; Clinical; •Clinical objective response rate (CR + PR); ; •Radiographic objective response rate by MRI (CR + PR); ; •Pathologic complete response rate (pCR); ; •Percentage of patients able to undergo breast‐conserving surgery; ; Molecular; •Change in HIF‐1a expression; ; Secondary Objective: •To estimate the rate of CHF in patients receiving TAC with or without bevacizumab ; •To estimate the rates of left ventricular ejection fraction (LVEF) changes as measured by either a decrease of > 15% from baseline, or > 10% to a value below the lower limit of normal (for the institution), in patients receiving TAC or TAC plus bevacizumab; •To investigate the clinical efficacy of TAC and TAC plus bevacizumab by estimating the clinical objective response rate (CR + PR), pathologic complete response rate (pCR), and rate of breast‐conserving surgery (BCS); •To estimate the rate of post‐surgical wound healing complications in patients who receive surgery after TAC or TAC plus bevacizumab; INCLUSION CRITERIA: 1.Female patient > 18 years 2.Histologically or cytologically proven adenocarcinoma of the breast 3.Stage II (minimum tumor size > 3 cm) or Stage III disease (except inflammatory breast cancer), as defined by the AJCC Staging Manual, 6th Edition, 2002 4.HER2‐negative disease (as defined by fluorescence in situ hybridization [FISH]) 5.ECOG performance status 0‐1 6.No prior chemotherapy, radiotherapy, or endocrine therapy for invasive or noninvasive breast cancer 7.Normal cardiac function (ejection fraction > lower limit of normal) as determined by MUGA or echocardiogram 8.If female of childbearing potential, pregnancy test is negative and willing to use effective contraception while on treatment and for at least 3 months after the last dose of study therapy 9.Patient is accessible and willing to comply with treatment and follow‐up 10.Patient is willing to provide written informed consent prior to the performance of any study‐related pr