Bevacizumab in Combination With Chemotherapy in the Neo-adjuvant Setting for HER2 (-) Breast Cancer

Inclusion Criteria:

* Female patients with histologic proven, corebiopsied, invasive ductal adenocarcinoma of the breast \>2 cm in size and of any N stage (clinical and/or radiological T-stage \> T1, including T4d), scheduled to receive preoperative chemotherapy.
* Age 18-70 years
* ECOG performance-status ≤1
* No prior or current neoplasm except for curatively treated non melanoma skin cancer, in situ carcinoma of the cervix
* No distant disease/secondary carcinoma
* Normal cardiac function
* Results of the following assessments at the time of inclusion must be available:

  1. bilateral Mammography (before enrolment)
  2. histology
  3. grading
  4. hormone-receptor-status
  5. HER2 status negative (is defined as FISH/CISH negative or IHC0 or IHC1+, or IHC2+ and FISH/CISH negative)
* Laboratory requirements (within 1 week before enrolment):

  1. Hematology: Neutrophils ≥ 1.5 x 109/l, Platelets ≥ 100 x 109/l, Hemoglobin\>11 g/dl
  2. Hepatic function: Total bilirubin \< 1 x ULN, SGOT and SGPT \< 1.5 x ULN, Alkaline phosphatases \< 1.5 x ULN. In case of abnormal values, the liver function tests have to be repeated within 3 days before study treatment.
  3. Renal function: Creatinine \< 1 x ULN
  4. Urinalysis: Urine dipstick of proteinuria \< 2+. Patients discovered to have ≥ 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate \<1 g of protein / 24 hours.
* Signed and dated Informed Consent before the start of specific protocol procedures
* If of childbearing potential, negative pregnancy test

Exclusion Criteria:

* Cytological only confirmation of diagnosis
* Lobular or other non-ductal types of breast cancer
* Pregnant, or lactating patients; patients of childbearing potential must implement adequate contraceptive measures during study participation
* Pre-existing motor or sensory neurotoxicity of a severity \> grade 2 by NCI-CTC AE
* Preoperative local treatment for breast cancer (i.e. incomplete surgery, radiotherapy)
* Prior or concurrent systemic antitumor therapy
* Evidence of wound healing complications, bone fracture, ulcer or the presence of clinically significant peripheral vascular disease
* Clinically significant cardiac disease e.g. congestive heart failure.
* Other serious illness or medical condition-uncontrolled hypertension or high risk uncontrolled arrythmias -history of significant neurologic or psychiatric disorders including psychotic disorders, dementia or seizures that would prohibit the understanding and giving of informed consent-active uncontrolled infection-unstable peptic ulcer, unstable diabetes mellitus or other contraindication for the use of corticosteroids
* Known hypersensitivity reaction to the compounds or incorporated substances.
* Evidence of bleeding diathesis or coagulopathy
* The use of full-dose oral or parenteral anticoagulants is permitted as long as the INR, or appropriate monitoring test is within therapeutic limits and the patient has been on a stable dose of anticoagulants for at least two weeks at the time of randomization. Patients not receiving anti coagulant medication must have an INR ≤ 1.5 an aPTT ≤ 1.5 x ULN within 7 days of randomization.
* Ongoing treatment with aspirin (\> 325mg / day) or other medications known to predispose to gastrointestinal ulceration.
* Major surgery (including open biopsy), significant traumatic injury within 28 days prior to enrolment.
* Minor surgery, including insertion of an indwelling catheter, within 24 hours prior to the first bevacizumab infusion
* Treatment with an investigational drug within 30 days prior to study entry.
* Legally incapacitated and/or other circumstances which make it undesirable for the subject to understand the nature, meaning and consequences of the clinical study