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High HER2 protein levels correlate with increased survival in breast cancer patients treated with anti‐HER2 therapy

Introduction: Current methods to determine HER2 (human epidermal growth factor receptor 2) status are affected by reproducibility issues and do not reliably predict benefit from anti‐HER2 therapy. Quantitative measurement of HER2 may more accurately identify breast cancer (BC) patients who will resp...

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Autores principales: Nuciforo, Paolo, Thyparambil, Sheeno, Aura, Claudia, Garrido-Castro, Ana, Vilaro, Marta, Peg, Vicente, Jimenez, José, Vicario, Rocio, Cecchi, Fabiola, Hoos, William, Burrows, Jon, Hembrough, Todd, Ferreres, Juan Carles, Perez-Garcia, José, Arribas, Joaquin, Cortes, Javier, Scaltriti, Maurizio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4968773/
https://www.ncbi.nlm.nih.gov/pubmed/26422389
http://dx.doi.org/10.1016/j.molonc.2015.09.002
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author Nuciforo, Paolo
Thyparambil, Sheeno
Aura, Claudia
Garrido-Castro, Ana
Vilaro, Marta
Peg, Vicente
Jimenez, José
Vicario, Rocio
Cecchi, Fabiola
Hoos, William
Burrows, Jon
Hembrough, Todd
Ferreres, Juan Carles
Perez-Garcia, José
Arribas, Joaquin
Cortes, Javier
Scaltriti, Maurizio
author_facet Nuciforo, Paolo
Thyparambil, Sheeno
Aura, Claudia
Garrido-Castro, Ana
Vilaro, Marta
Peg, Vicente
Jimenez, José
Vicario, Rocio
Cecchi, Fabiola
Hoos, William
Burrows, Jon
Hembrough, Todd
Ferreres, Juan Carles
Perez-Garcia, José
Arribas, Joaquin
Cortes, Javier
Scaltriti, Maurizio
author_sort Nuciforo, Paolo
collection PubMed
description Introduction: Current methods to determine HER2 (human epidermal growth factor receptor 2) status are affected by reproducibility issues and do not reliably predict benefit from anti‐HER2 therapy. Quantitative measurement of HER2 may more accurately identify breast cancer (BC) patients who will respond to anti‐HER2 treatments. Methods: Using selected reaction monitoring mass spectrometry (SRM‐MS), we quantified HER2 protein levels in formalin‐fixed, paraffin‐embedded (FFPE) tissue samples that had been classified as HER2 0, 1+, 2+ or 3+ by immunohistochemistry (IHC). Receiver operator curve (ROC) analysis was conducted to obtain optimal HER2 protein expression thresholds predictive of HER2 status (by standard IHC or in situ hybridization [ISH]) and of survival benefit after anti‐HER2 therapy. Results: Absolute HER2 amol/μg levels were significantly correlated with both HER2 IHC and amplification status by ISH (p < 0.0001). A HER2 threshold of 740 amol/μg showed an agreement rate of 94% with IHC and ISH standard HER2 testing (p < 0.0001). Discordant cases (SRM‐MS‐negative/ISH‐positive) showed a characteristic amplification pattern known as double minutes. HER2 levels >2200 amol/μg were significantly associated with longer disease‐free survival (DFS) and overall survival (OS) in an adjuvant setting and with longer OS in a metastatic setting. Conclusion: Quantitative HER2 measurement by SRM‐MS is superior to IHC and ISH in predicting outcome after treatment with anti‐HER2 therapy.
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spelling pubmed-49687732016-08-01 High HER2 protein levels correlate with increased survival in breast cancer patients treated with anti‐HER2 therapy Nuciforo, Paolo Thyparambil, Sheeno Aura, Claudia Garrido-Castro, Ana Vilaro, Marta Peg, Vicente Jimenez, José Vicario, Rocio Cecchi, Fabiola Hoos, William Burrows, Jon Hembrough, Todd Ferreres, Juan Carles Perez-Garcia, José Arribas, Joaquin Cortes, Javier Scaltriti, Maurizio Mol Oncol Articles Introduction: Current methods to determine HER2 (human epidermal growth factor receptor 2) status are affected by reproducibility issues and do not reliably predict benefit from anti‐HER2 therapy. Quantitative measurement of HER2 may more accurately identify breast cancer (BC) patients who will respond to anti‐HER2 treatments. Methods: Using selected reaction monitoring mass spectrometry (SRM‐MS), we quantified HER2 protein levels in formalin‐fixed, paraffin‐embedded (FFPE) tissue samples that had been classified as HER2 0, 1+, 2+ or 3+ by immunohistochemistry (IHC). Receiver operator curve (ROC) analysis was conducted to obtain optimal HER2 protein expression thresholds predictive of HER2 status (by standard IHC or in situ hybridization [ISH]) and of survival benefit after anti‐HER2 therapy. Results: Absolute HER2 amol/μg levels were significantly correlated with both HER2 IHC and amplification status by ISH (p < 0.0001). A HER2 threshold of 740 amol/μg showed an agreement rate of 94% with IHC and ISH standard HER2 testing (p < 0.0001). Discordant cases (SRM‐MS‐negative/ISH‐positive) showed a characteristic amplification pattern known as double minutes. HER2 levels >2200 amol/μg were significantly associated with longer disease‐free survival (DFS) and overall survival (OS) in an adjuvant setting and with longer OS in a metastatic setting. Conclusion: Quantitative HER2 measurement by SRM‐MS is superior to IHC and ISH in predicting outcome after treatment with anti‐HER2 therapy. John Wiley and Sons Inc. 2015-09-15 2016-01 /pmc/articles/PMC4968773/ /pubmed/26422389 http://dx.doi.org/10.1016/j.molonc.2015.09.002 Text en © 2016 The Authors. Published by FEBS Press and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Articles
Nuciforo, Paolo
Thyparambil, Sheeno
Aura, Claudia
Garrido-Castro, Ana
Vilaro, Marta
Peg, Vicente
Jimenez, José
Vicario, Rocio
Cecchi, Fabiola
Hoos, William
Burrows, Jon
Hembrough, Todd
Ferreres, Juan Carles
Perez-Garcia, José
Arribas, Joaquin
Cortes, Javier
Scaltriti, Maurizio
High HER2 protein levels correlate with increased survival in breast cancer patients treated with anti‐HER2 therapy
title High HER2 protein levels correlate with increased survival in breast cancer patients treated with anti‐HER2 therapy
title_full High HER2 protein levels correlate with increased survival in breast cancer patients treated with anti‐HER2 therapy
title_fullStr High HER2 protein levels correlate with increased survival in breast cancer patients treated with anti‐HER2 therapy
title_full_unstemmed High HER2 protein levels correlate with increased survival in breast cancer patients treated with anti‐HER2 therapy
title_short High HER2 protein levels correlate with increased survival in breast cancer patients treated with anti‐HER2 therapy
title_sort high her2 protein levels correlate with increased survival in breast cancer patients treated with anti‐her2 therapy
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4968773/
https://www.ncbi.nlm.nih.gov/pubmed/26422389
http://dx.doi.org/10.1016/j.molonc.2015.09.002
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