ERBB2 phosphorylation and trastuzumab sensitivity of breast cancer cell lines.

Breast cancers that overexpress the ERBB2 tyrosine kinase receptor may be treated with the recombinant humanized monoclonal anti-ERBB2 antibody trastuzumab (herceptin). However, resistance to this targeted therapy is frequent. We have determined the response of 18 breast tumor cell lines to trastuzumab and compared it with the ERBB2 phosphorylation status using antibodies directed against tyrosine residue 1248. We show that sensitivity to trastuzumab is frequently associated with the expression of a phosphorylated ERBB2 protein.