PMID- 20178580
OWN - NLM
STAT- MEDLINE
DCOM- 20101228
LR  - 20211020
IS  - 1471-2407 (Electronic)
IS  - 1471-2407 (Linking)
VI  - 10
DP  - 2010 Feb 23
TI  - Differential survival following trastuzumab treatment based on quantitative HER2 
      expression and HER2 homodimers in a clinic-based cohort of patients with 
      metastatic breast cancer.
PG  - 56
LID - 10.1186/1471-2407-10-56 [doi]
AB  - BACKGROUND: We have recently described the correlation between quantitative 
      measures of HER2 expression or HER2 homodimers by the HERmark assay and objective 
      response (RR), time-to progression (TTP), and overall survival (OS) in an 
      expanded access cohort of trastuzumab-treated HER2-positive patients with 
      metastatic breast cancer (MBC) who were stringently selected by fluorescence in 
      situ hybridization (FISH). Multivariate analyses suggested a continuum of HER2 
      expression that correlated with outcome following trastuzumab. Here we 
      investigate the relationship between HER2 expression or HER2 homodimers and OS in 
      a clinic-based population of patients with MBC selected primarily by IHC. 
      METHODS: HERmark, a proximity-based assay designed to detect and quantitate 
      protein expression and dimerization in formalin-fixed paraffin-embedded (FFPE) 
      tissues, was used to measure HER2 expression and HER2 homodimers in FFPE samples 
      from patients with MBC. Assay results were correlated with OS using univariate 
      Kaplan-Meier, hazard function plots, and multivariate Cox regression analyses. 
      RESULTS: Initial analyses revealed a parabolic relationship between continuous 
      measures of HER2 expression and risk of death, suggesting that the assumption of 
      linearity for the HER2 expression measurements may be inappropriate in subsequent 
      multivariate analyses. Cox regression analyses using the categorized variable of 
      HER2 expression level demonstrated that higher HER2 levels predicted better 
      survival outcomes following trastuzumab treatment in the high HER2-expressing 
      group. CONCLUSIONS: These data suggest that the quantitative amount of HER2 
      expression measured by Hermark may be a new useful marker to identify a more 
      relevant target population for trastuzumab treatment in patients with MBC.
FAU - Toi, Masakazu
AU  - Toi M
AD  - Faculty of Medicine, Kyoto University, Kyoto, Japan. toi@kuhp.kyoto-u.ac.jp
FAU - Sperinde, Jeff
AU  - Sperinde J
FAU - Huang, Weidong
AU  - Huang W
FAU - Saji, Shigehira
AU  - Saji S
FAU - Winslow, John
AU  - Winslow J
FAU - Jin, Xueguang
AU  - Jin X
FAU - Tan, Yuping
AU  - Tan Y
FAU - Ohno, Shinji
AU  - Ohno S
FAU - Nakamura, Seigo
AU  - Nakamura S
FAU - Iwata, Hiroji
AU  - Iwata H
FAU - Masuda, Norikazu
AU  - Masuda N
FAU - Aogi, Kenjiro
AU  - Aogi K
FAU - Morita, Satoshi
AU  - Morita S
FAU - Petropoulos, Christos
AU  - Petropoulos C
FAU - Bates, Michael
AU  - Bates M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100223
PL  - England
TA  - BMC Cancer
JT  - BMC cancer
JID - 100967800
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - P188ANX8CK (Trastuzumab)
SB  - IM
MH  - Antibodies, Monoclonal/*therapeutic use
MH  - Antibodies, Monoclonal, Humanized
MH  - Breast Neoplasms/*drug therapy/*mortality/pathology
MH  - Cohort Studies
MH  - Dimerization
MH  - Disease Progression
MH  - Female
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Multivariate Analysis
MH  - Neoplasm Metastasis
MH  - Proportional Hazards Models
MH  - Receptor, ErbB-2/*biosynthesis/*chemistry
MH  - Trastuzumab
MH  - Treatment Outcome
PMC - PMC2837013
EDAT- 2010/02/25 06:00
MHDA- 2010/12/29 06:00
PMCR- 2010/02/23
CRDT- 2010/02/25 06:00
PHST- 2009/04/15 00:00 [received]
PHST- 2010/02/23 00:00 [accepted]
PHST- 2010/02/25 06:00 [entrez]
PHST- 2010/02/25 06:00 [pubmed]
PHST- 2010/12/29 06:00 [medline]
PHST- 2010/02/23 00:00 [pmc-release]
AID - 1471-2407-10-56 [pii]
AID - 10.1186/1471-2407-10-56 [doi]
PST - epublish
SO  - BMC Cancer. 2010 Feb 23;10:56. doi: 10.1186/1471-2407-10-56.