Efficacy and Safety of Bevacizumab in the Neodjuvant Treatment of Inflammatory Breast Cancer

Inclusion Criteria:

* • Patients must have signed a written informed consent form prior to any study specific procedures,

  * Women,
  * 20 years or older,
  * Performance status \< 2 (ECOG),
  * Histologically confirmed inflammatory breast cancer T4d any N,
  * hormonal Status known,
  * no metastases according to the last TNM classification,
  * adequate hematologic function :

    * absolute neutrophil count ≥ 1 500/mm3
    * Platelets ≥ 100 000/mm3
    * Hemoglobin ≥ 9 g/dL
  * adequate liver function :

    * ASAT and ALAT \< à 3 ULN
    * Alkaline Phosphatase \< 5 ULN
    * Total bilirubin \< 1,5 ULN, o
  * adequate kidney function :

    * creatinine \< 1,5 x normal or creatinine Clearance ≥ 50ml/min (according to the cockcroft and Gault formula)
    * Urine Dipstick for proteinuria \< 2+ patients who have proteinuria ≥ 2 + on dipstick urinalysis at baseline should undergo a 24 hours urine collection and must demonstrate ≤ 1 g of protein in 24 hours,
  * adequate coagulation and cardiac function :

    * Prothrombin ratio ≥ 70 % and,
    * Prothrombin time ≤ 1,5 upper limit of normal (ULN) within 7 days prior to enrolment
    * Left Ventricular ejection fraction (LVEF) ≥ 55 %

Exclusion Criteria:

* Patients of childbearing potential with a positive pregnancy test (serum or urine) prior to enrollment
* Patients who are either not post-menopausal, or surgically sterile, not using "effective contraception" (the definition of "effective contraception" will be based on the judgment of the investigator)
* Patients who are pregnant or breastfeeding
* Patient considered socially or psychological unable to comply with the treatment and the required medial follow-up,
* Concurrent participation in another clinical trial or treatment with any other anticancer agent during the protocol specified period
* Patients unwilling or unable to sign and date an Ethics Committee (EC)/ Institutional Review Board (IRB)-approved patient informed consent form
* Patients unwilling or unable to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
* Non inflammatory breast cancer with lymphatic skin permeation, Metastases,
* Bilateral breast cancer
* Distant metastases (stage IV)
* History of another cancer other than adequately treated carcinoma in situ of the cervix uteri, basal or squamous cell skin cancer
* Prior anti tumor therapy (surgery, radiotherapy, chemotherapy, hormonal treatment and targeted therapy) except treatments given for carcinoma in situ of the cervix uteri, basal or squamous cell skin cancer
* History or evidence of inherited bleeding diathesis or coagulopathy,
* History of thrombotic disorders within the last 6 months prior to enrollment (i.e. cerebrovascular accident, transient ischemic attacks, subarachnoid hemorrhage),
* Uncontrolled hypertension (systolic \> 150 mmHg and/or diastolic \> 100 mmHg)with or without any anti-hypertensive medication ; patients with high initial blood pressure are eligible if entry criteria are met after initiation or adjustment of anti-hypertensive medication,
* Any of the following within 6 months prior to enrollment:

myocardial infarction, severe/unstable angina, or coronary/peripheral artery bypass graft surgery, clinically symptomatic and uncontrolled cardiovascular disease, or clinically significant cardiac arrhythmias (grade 3-4)

* Severe resting dyspnea due to complications or oxygen dependency,
* Diabetic patient treated with oral anti-diabetics or insulin with an underlying cardiopathy at ultrasound,
* Any other severe acute illness such as active uncontrolled infections that would preclude the safe administration of study therapy at the time of the enrolment
* Other severe underlying medical conditions, which could impair the ability to participate in the study
* Major surgery, significant traumatic injury within 28 days prior to study treatment start or anticipation of the need for major surgery during study treatment,
* Minor surgery, including insertion of an indwelling catheter, within 24 hours prior to the first bevacizumab infusion,
* Non-healing wound, active peptic ulcer or bone fracture,
* History of abdominal fistula, diagnosed with a trachea-oesophageal fistula or any grade 4 non gastro-intestinal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months of enrolment,