Vinorelbine Metronomic Plus Lapatinib for Overexpressing HER-2 Metastatic Breast Cancer

Inclusion Criteria: * Histologically- or cytologically- confirmed metastatic breast adenocarcinoma * Age 18-75 years * HER2 status positive according to the local institution reported grade 3+ staining intensity (on a scale of 0 to 3) by means of immunohistochemical analysis or grade 2+ staining intensity by means of immunohistochemical analysis with gene amplification on fluorescence in situ hybridization * Previous therapies had to include, regimens containing an anthracycline and a taxane * Previous treatment with trastuzumab, alone or in combination with chemotherapy for locally advanced or metastatic disease, is required * 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 upper normal limit in the presence of liver metastases); adequate renal function (serum creatinine \<1.5 times the upper normal limit); and bone marrow (neutrophils ≥ 1.5x 109 /L, and platelets ≥ 100x 109 /L) function * No radiation of measurable disease (except brain metastases) * No progressive brain metastases according to clinical or radiological criteria * No brain metastases without prior radiation therapy * Written informed consent Exclusion Criteria: * Patient unable to take oral medication * Active infection * History of significant cardiac disease (unstable angina, congestive heart failure, myocardial infarction within the previous 6 months, ventricular arrhythmias) * Other invasive malignancy except nonmelanoma skin cancer * Psychiatric illness or social situation that would preclude study compliance * Pregnant or lactating women