Quantitative Measurements Of p95 Protein Expression In Tumors From Patients With Metastatic Breast Cancer Treated With Trastuzumab

Background: Expression of p95 in HER2-positive breast cancer is potentially a major determinant of trastuzumab resistance because p95 lacks the trastuzumab binding site while retaining kinase activity. Previously, an optimal clinical cutoff for a continuous measurement of p95 expression was defined in a training set of trastuzumabtreated MBC patients (Clin Cancer Res, 16:4226, 2010).

Methods: Quantitative H2T (HERmark® HER2-total) and p95 assays (VeraTag®, Monogram Biosciences) were retrospectively performed on formalin-fixed, paraffinembedded tumors from an independent series of 240 trastuzumab-treated MBC patients. The pre-specified cutoff for p95 was tested to determine whether p95 above the cutoff in the HER2-positive subset correlated with worse progression-free survival (PFS) and overall survival (OS), as was observed in the training set. P95 expression was also assessed by immunohistochemistry (IHC) using the same antibody as the p95 VeraTag assay.