title: Quantitative measurements of tumoral p95HER2 protein expression in metastatic breast cancer patients treated with trastuzumab: independent validation of the p95HER2 clinical cutoff.
abstract: OBJECTIVE
  P95HER2 (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.
  
  
  METHODS
  In 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.
  
  
  RESULTS
  In 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.
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: 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.
authors.forename: Renata
authors.initials: R
authors.lastname: Duchnowska
authors.affiliation: 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.
authors.forename: Jeff
authors.initials: J
authors.lastname: Sperinde
authors.affiliation: 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.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Chenna
authors.affiliation: 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.
authors.forename: Mojgan
authors.initials: M
authors.lastname: Haddad
authors.affiliation: 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.
authors.forename: Agnes
authors.initials: A
authors.lastname: Paquet
authors.affiliation: 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.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Lie
authors.affiliation: 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.
authors.forename: Jodi M
authors.initials: JM
authors.lastname: Weidler
authors.affiliation: 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.
authors.forename: Weidong
authors.initials: W
authors.lastname: Huang
authors.affiliation: 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.
authors.forename: John
authors.initials: J
authors.lastname: Winslow
authors.affiliation: 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.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Jankowski
authors.affiliation: 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.
authors.forename: Bogumiła
authors.initials: B
authors.lastname: Czartoryska-Arłukowicz
authors.affiliation: 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.
authors.forename: Piotr J
authors.initials: PJ
authors.lastname: Wysocki
authors.affiliation: 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.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Foszczyńska-Kłoda
authors.affiliation: 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.
authors.forename: Barbara
authors.initials: B
authors.lastname: Radecka
authors.affiliation: 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.
authors.forename: Maria M
authors.initials: MM
authors.lastname: Litwiniuk
authors.affiliation: 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.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Zok
authors.affiliation: 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.
authors.forename: Michał
authors.initials: M
authors.lastname: Wiśniewski
authors.affiliation: 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.
authors.forename: Dorota
authors.initials: D
authors.lastname: Zuziak
authors.affiliation: 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.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Biernat
authors.affiliation: 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 jjassem@gumed.edu.pl.
authors.forename: Jacek
authors.initials: J
authors.lastname: Jassem
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000276:immunology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000276:immunology / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D018572:Disease-Free Survival; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011237:Predictive Value of Tests; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism; D015203:Reproducibility of Results; D012189:Retrospective Studies; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D047628:Estrogen Receptor alpha; D018719:Erb-b2 Receptor Tyrosine Kinases; D011980:Receptors, Progesterone; D000068878:Trastuzumab