Inclusion Criteria:

- Histologically- or cytologically- confirmed metastatic breast adenocarcinoma

- No HER2 overexpression or gene amplification

- No previous therapy for metastatic breast cancer is allowed

- Age 18-75 years

- At least 12 months interval since prior adjuvant therapy with taxanes and/or
anthracyclines

- Measurable disease as defined by the presence of at least one measurable lesion
(except bone metastases, ascites or pleural effusions)

- Performance status (WHO) 0-2

- Adequate liver (serum bilirubin <1.5 times the upper normal limit, AST and ALT <2.5
times the upper normal limit in the absence of demonstrable liver metastases, or <5
times the UNL in the presence of liver metastases)

- Adequate renal function (serum creatinine <1.5 times the upper normal limit

- Adequate bone marrow function (neutrophils ≥ 1.5x 109 /L, and platelets ≥ 100x 109
/L)

- Written informed consent

Exclusion Criteria:

- Active infection

- Brain metastases

- History of significant cardiac disease (unstable angina, congestive heart failure,
myocardial infarction within the previous 6 months, ventricular arrhythmias)

- History of stroke

- Anticoagulation therapy (except of low dose aspirin <325mg)

- Other invasive malignancy except nonmelanoma skin cancer

- Psychiatric illness or social situation that would preclude study compliance

- Pregnant or lactating women