• Renata Duchnowska, Jeff Sperinde, Ahmed Chenna, Mojgan Haddad, Agnes Paquet, Yolanda Lie, Jodi M Weidler, Weidong Huang, John Winslow, Tomasz Jankowski, Bogumiła Czartoryska-Arłukowicz, Piotr J Wysocki, Małgorzata Foszczyńska-Kłoda, Barbara Radecka, Maria M Litwiniuk, Jolanta Zok, Michał Wiśniewski, Dorota Zuziak, Wojciech Biernat, and Jacek Jassem.
• Authors' Affiliations: Military Institute of Medicine, Warsaw; Lublin Oncology Center, Lublin; Białystok Oncology Center, Białystok; Greater Poland Cancer Center, Poznań; West Pomeranian Oncology Center, Szczecin; Opole Oncology Center, Opole; Warmia and Masuria Oncology Center, Olsztyn; Bydgoszcz Oncology Center, Bydgoszcz; Beskidy Oncology Center, Bielsko-Biała; Medical University of Gdańsk, Gdańsk, Poland; and Monogram Biosciences, Inc., South San Francisco, California.
• Clin Cancer Res. 2014 May 15; 20 (10): 2805-13.

PurposeP95HER2 (p95) is a truncated form of the HER2, which lacks the trastuzumab-binding site and contains a hyperactive kinase domain. Previously, an optimal clinical cutoff of p95 expression for progression-free survival (PFS) and overall survival (OS) was defined using a quantitative VeraTag assay (Monogram Biosciences) in a training set of trastuzumab-treated metastatic breast cancer (MBC) patients.Experimental DesignIn the current study, the predictive value of the p95 VeraTag assay cutoff established in the training set was retrospectively validated for PFS and OS in an independent series of 240 trastuzumab-treated MBC patients from multiple institutions.ResultsIn the subset of 190 tumors assessed as HER2-total (H2T)-positive using the quantitative HERmark assay (Monogram Biosciences), p95 VeraTag values above the predefined cutoff correlated with shorter PFS (HR = 1.43; P = 0.039) and shorter OS (HR = 1.94; P = 0.0055) where both outcomes were stratified by hormone receptor status and tumor grade. High p95 expression correlated with shorter PFS (HR = 2.41; P = 0.0003) and OS (HR = 2.57; P = 0.0025) in the hormone receptor-positive subgroup of patients (N = 78), but not in the hormone receptor-negative group. In contrast with the quantitative p95 VeraTag measurements, p95 immunohistochemical expression using the same antibody was not significantly correlated with outcomes.ConclusionsThe consistency in the p95 VeraTag cutoff across different cohorts of patients with MBC treated with trastuzumab justifies additional studies using blinded analyses in larger series of patients.©2014 American Association for Cancer Research.

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