A specific vascular endothelial growth factor receptor tyrosine kinase inhibitor enhances the antiproliferative effect of trastuzumab in human epidermal growth factor receptor 2 overexpressing breast cancer cell lines.

Background: Trastuzumab has been found to have potent antiproliferative effects in human epidermal growth factor receptor 2 (HER-2)-overexpressing human breast tumors. Inhibition of vascular endothelial growth factor receptor (VEGFR), a protein often overexpressed in breast carcinoma, has been shown to induce apoptosis.

Methods: Breast carcinoma cell lines were cultured with increasing doses of trastuzumab and/or a VEGFR tyrosine kinase inhibitor (TKI). Growth inhibition and apoptosis were assessed after 5 days and 48 hours of treatment, respectively. Combination index values were calculated to determine the effectiveness of this drug combination.

Results: A dose-dependent growth inhibition was shown in all cell lines tested with the VEGFR TKI, whereas trastuzumab was effective only in the HER-2-positive cells. A synergistic interaction was shown in the HER-2-overexpressing cell lines, accompanied by an increase in apoptosis.

Conclusions: The combination of trastuzumab and a VEGFR TKI may be of therapeutic value in select breast cancer patients.