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Comparison of different approaches for assessment of HER2 expression on protein and mRNA level : prediction of chemotherapy response in the neoadjuvant GeparTrio trial ( NCT00544765 ) . Human epidermal growth factor receptor 2 ( HER2 ) testing is an essential part of pathological assessment in breast cancer patients , as HER2 provides not only prognostic but also predictive information on response to targeted therapy . So far , HER2 test accuracy of immunohistochemistry/in situ-hybridization techniques is still under debate , and more reliable and robust technologies are needed . To address this issue and to evaluate the predictive value of HER2 on chemotherapy , we investigated a cohort of 278 patients from the GeparTrio trial , a prospective neoadjuvant anthracycline/taxane-based multicenter study . In the GeparTrio trial , patients were not treated with any anti-HER2 therapy , as this was not standard therapy at this time . The HER2 status was analyzed by three different approaches : local and central evaluation using immunohistochemistry combined with in situ-hybridization as well as evaluation of HER2 mRNA expression using kinetic RT-PCR from formalin-fixed , paraffin-embedded ( FFPE ) tissue samples using a predefined cutoff . HER2 overexpression/amplification was observed in 37.3 % ( 91/244 ) and 17.9 % ( 41/229 ) of the informative samples in the local and central evaluations , respectively . Positive HER2 mRNA levels were found in 19.8 % ( 55/278 ) . We observed a highly significant correlation between central HER2 expression and HER2 status measured by kinetic RT-PCR ( r = 0.856 , P < 0.0001 ) and an overall agreement of 95.6 % ( κ statistic , 0.862 , CI 0.77-0.94 ) . Further , central HER2 as well as HER2 mRNA expression were predictors for a pathological complete response after neoadjuvant anthracycline/taxane-based primary chemotherapy in a univariate binary logistic regression analysis ( OR 3.29 , P = 0.002 ; OR 2.65 , P = 0.004 ) . The predictive value could be confirmed for the central HER2 status by multivariate analysis ( OR 3.04 , P = 0.027 ) . The locally assessed HER2 status was not predictive of response to chemotherapy . Our results suggest that standardized methods are preferable for evaluation of HER2 status . The kinetic RT-PCR from FFPE tissue might be an additional approach for assessment of this important prognostic and predictive parameter but has to be confirmed by other studies .
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Intervention_Pharmacological
chemotherapy
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Intervention_Pharmacological
Human epidermal growth factor receptor 2
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Intervention_Pharmacological
chemotherapy
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Intervention_Pharmacological
anti-HER2 therapy
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Intervention_Physical
immunohistochemistry
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Intervention_Physical
in situ-hybridization
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Intervention_Physical
kinetic RT-PCR
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Outcome_Physical
HER2 status
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Outcome_Physical
HER2 mRNA expression
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Outcome_Physical
HER2 overexpression/amplification
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Outcome_Physical
Positive HER2 mRNA levels
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Outcome_Physical
correlation between central HER2 expression
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Outcome_Physical
HER2 status measured by kinetic RT-PCR
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Participant_Condition
breast cancer
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Participant_Sample-size
278