Inclusion Criteria:

1. Written informed consent

2. Complete baseline documentation sent to GBG Forschungs GmbH;

3. Unilateral or bilateral primary carcinoma of the breast, confirmed histologically by
core biopsy. Fine-needle aspiration is not sufficient. Incisional biopsy is not
allowed.

4. Tumor lesion in the breast with a palpable size of ≥ 2 cm or a sonographically size
of at least 1 cm in maximum diameter. The lesion has to be measurable in
two-dimensions preferably by sonography. In case of inflammatory disease the extent
of inflammation can be used as measurable lesion;

5. Patients should have stages of disease in which adjuvant chemotherapy would be
considered.

- Locally advanced tumors with cT4 or cT3 or

- Estrogen (ER)- and progesterone (PgR)-receptor negative tumors or

- ER or PgR positive tumors which are cN+ (for cT2) or pNSLN+ (for cT1) * During
the Run-In-Safety phase only patients with cT4 or cT3 cN+ disease are eligible.

6. Known HER-2/neu status detected on core biopsy. HER-2/neu positive is defined as
HercepTest IHC 3+ or FISH+;

7. Age older than 18 years;

8. Karnofsky Performance status index at least 80%;

9. Normal cardiac function must be confirmed by ECG and cardiac ultrasound (LVEF or
shortening fraction) within 1 month prior to registration.

10. Laboratory requirements:

Hematology: Absolute neutrophil count (ANC) ≥ 2.0 x 10e9/L platelets ≥ 100 x 10e9/L,
Hemoglobin ≥ 10 g/dL (≥ 6.2 mmol/L) Hepatic function: Total bilirubin < 1 x UNL ASAT
(SGOT) and ALAT (SGPT)≤ 2.5 x UNL Alkaline phosphatase ≤ 5 UNL. Patients with ASAT
and / or ALAT > 1.5 x UNL associated with alkaline phosphatase > 2.5 x UNL are not
eligible for the study; Renal function: Creatinine ≤ 175 µmol/L (2 mg/dL) < 1,25 UNL
(or the calculated creatinine clearance ≥ 60 mL/min) Urine dipstick for proteinuria <
2+. Patients discovered to have ≥2+ proteinuria on dipstick urinalysis should undergo
a 24 hour urine collection and must demonstrate ≤1 g of protein in 24 hours

11. Paraffin tumor tissue block and two serum samples centrally made available

12. Negative pregnancy test (urine or serum)

13. Complete staging work-up within 3 months prior to registration.

14. Patients must be available and compliant for treatment and follow-up.

Exclusion criteria:

1. Patients with low or moderate risk, which are only doubtful candidates for adjuvant
chemotherapy

2. Evidence of distant metastasis;

3. Prior chemotherapy for any malignancy;

4. Prior radiation therapy for breast cancer;

5. Pregnant or lactating patients.

6. Inadequate general condition

7. Previous malignant disease

8. Known or suspected congestive heart failure (>NYHA I) and/or coronary heart disease,
angina pectoris requiring antianginal medication, previous history of myocardial
infarction, evidence of transmural infarction on ECG, un- or poorly controlled
arterial hypertension, rhythm abnormalities requiring permanent treatment, clinically
significant valvular heart disease

9. Previous thromboembolic event

10. Known hemorrhagic diathesis or increased bleeding risk

11. History of significant neurological or psychiatric disorders that would prohibit the
understanding and giving of informed consent;

12. Pre-existing motor or sensory neuropathy of a severity more than grade 2 by NCI
criteria

13. Currently active infection;incomplete wound healing

14. Active peptic ulcer

15. Disease significantly affecting gastrointestinal function

16. History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess
within 6 months of enrollment

17. Severe pulmonary condition/illness

18. Unstable diabetes mellitus; insulin dependent type II diabetes mellitus

19. Major surgery or incomplete wound healing within the last 28 days

20. Definite contraindications for the use of corticosteroids

21. Known hypersensitivity reaction to one of the investigational compounds or
incorporated substances; or known dihydropyrimidine dehydrogenase deficiency

22. Concurrent treatment with:chronic corticosteroids unless initiated > 6 months prior
to study entry and at low dose (20 mg methylprednisolone or equivalent); sex
hormones.Virostatic agents like sorivudine or analogs like brivudine, concurrent
treatment with aminoglycosides; anticoagulants: heparin, warfarin as well as acetic
acid (e.g. Aspirin®) at a dose of > 325mg/day or clopidogrel at a dose of > 75
mg/day)e.other experimental drugs or any other anti-cancer therapy; drugs recognized
as being strong inhibitors or inducers of the isoenzyme CYP3A (e.g. Rifabutin,
Rifampicin, Clarithromycin, Ketoconazole, Itraconazole, Ritonavir, Telithromycin,
Erythromycin, Verapamil, Dilitazem, within the last 5 days or the expected need for
these treatments during study participation.