A Phase II Study of Neoadjuvant Trastuzumab+Docetaxel+NPLD+/-Bevacizumab in Her2-pos. Early Breast Cancer

Inclusion Criteria:

* Female or male, age ≥ 18 years
* Pathologically confirmed invasive primary breast adenocarcinoma (except inflammatory breast cancer, T4d) scheduled for taxane containing neoadjuvant systemic treatment with/without palpable lymph nodes.
* Documented HER2 protein overexpression as determined by immunohistochemistry (IHC) 3+ or by demonstrated HER2/c-erbB2 gene amplification of the primary tumor by a local laboratory.
* LVEF ≥ 55% measured by echocardiography or MUGA within 4 weeks before randomization
* ECOG Performance Status ≤ 1
* Able and willing to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
* Written Informed Consent

Exclusion Criteria:

Current Treatment

* Requirement for concurrent use of the antiviral agent sorivudine or chemically related analogues, such as brivudine.
* Chronic daily treatment with corticosteroids excl. inhaled steroids.
* Chronic daily treatment with aspirin and aspirin analogs or clopidogrel
* Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to randomization or anticipation of need for major surgery during the course of study treatment
* Current or recent (within 30 days prior to randomization) treatment with another investigational drug or participation in another investigational study.

Laboratory

* Inadequate bone marrow function
* Inadequate liver function
* Inadequate renal function
* Patients not receiving anticoagulant medication who have activated partial thromboplastin time (aPTT) within 7 days prior to Day1 of the cycle 1.

Concomitant Conditions

* Other malignancy within the last 5 years before randomization except for curatively treated carcinoma in situ of the cervix or non-melanomatous skin cancer
* Evidence of distant metastasis judged clinically and at least by chest-X-ray, liver-sonography and bone scan. If there is any clinical suspicion of brain metastasis, a CT-scan or MRI of the brain must be conducted within 4 weeks prior to randomization.
* Serious concurrent disease which could affect compliance with the protocol or interpretation of results, including, but not limited to:

  * Active infection requiring i.v. antibiotics
  * Uncontrolled hypertension
  * Clinically significant history of cardiovascular disease as indicated by: cerebrovascular accident or stroke; myocardial infarction; unstable angina; NYHA Grade II or greater CHF; cardiac arrhythmia requiring medication; clinically significant valvular heart disease.
  * Dyspnea at rest necessitating supportive oxygen therapy or with significant pleural effusions
  * Poorly controlled diabetes mellitus
  * History or evidence upon physical/neurological examination of CNS disease unrelated to cancer (e.g. uncontrolled seizures) unless adequately treated with standard medical therapy
  * History or evidence of inherited bleeding diathesis or coagulopathy with the risk of bleeding
  * History of abdominal fistula, GI perforation, or intra-abdominal abscess within 6 months of randomization
  * Serious non-healing wound, peptic ulcer, or bone fracture
  * Clinically significant malabsorption syndrome, ulcerative colitis, disease affecting GI function, resection of the stomach or small bowel, or inability to take oral medication
  * Uncorrected hypokalemia or hypomagnesemia
  * Organ allografts requiring immunosuppressive therapy
* Evidence of any other disease, metabolic or psychological dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, may affect patient compliance with study routines, or place the patient at high risk from treatment related complications.
* Known hypersensitivity to any of the study drugs/excipients.
* Hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies.

Other

* Pregnant, lactating females or women of childbearing potential without a negative pregnancy test
* Fertile males or females of childbearing potential
* Patients not accessible for treatment or follow-up