Clinical Cancer esearch ing , Diagnosis , Prognosis ntitation of p 95 HER 2 in Paraffin Sections by Using a-Specific Antibody and Correlation with Outcome in R ohort of Trastuzumab-Treated Breast Cancer Patients

wnloaded pose: p95HER2 is an NH2-terminally truncated form of HER2 that lacks the trastuzumab binding d is therefore thought to confer resistance to trastuzumab treatment. In this report, we introduce a ntibody that has enabled the first direct quantitative measurement of p95HER2 in formalin-fixed in-embedded (FFPE) breast cancer tissues. We sought to show that quantitative p95HER2 levels correlate with outcome in trastuzumab-treated HER2-positive metastatic breast cancer. erimental Design: The novel p95HER2 antibody used here was characterized for sensitivity, spec, and selectivity over full-length HER2. Quantitative p95HER2 levels were measured in 93 metastatic tumors using a VeraTag FFPE assay to determine the correlation of p95HER2 levels with outcomes. ults: Within a cohort of trastuzumab-treated metastatic breast cancer patients, high levels of ER2 were found to correlate with shorter progression-free survival [hazard ratio (HR), 1.9; P = ] and overall survival (HR, 2.2; P = 0.012) in patients with tumors selected to be HER2 positive VeraTag HER2 assay. For those with tumors found to be fluorescence in situ hybridization positive, ed p95HER2 correlated similarly with shorter progression-free survival (HR, 1.8; P = 0.022) and l survival (HR, 2.2; P = 0.009). clusions: We have successfully generated an antibody that can specifically detect p95HER2, eveloped an assay to quantify expression in FFPE tumor specimens. Using this novel assay, ve identified a group of HER2-positive patients expressing p95HER2 that have a worse outcome on trastuzumab. As p95HER2 retains sensitivity to kinase inhibitors, measurement of p95HER2 while in breast tumor sections may be useful in guiding treatment for patients with HER2-positive breast cancer.