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

Paolo Nuciforo; Sheeno Thyparambil; Claudia Aura; Ana Garrido-Castro; Marta Vilaro; Vicente Peg; José Jimenez; Rocio Vicario; Fabiola Cecchi; William Hoos; Jon Burrows; Todd Hembrough; Juan Carles Ferreres; José Perez-Garcia; Joaquin Arribas; Javier Cortes; Maurizio Scaltriti

doi:https://doi.org/10.1016/j.molonc.2015.09.002

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

Paolo Nuciforo, Sheeno Thyparambil, Claudia Aura, Ana Garrido-Castro, Marta Vilaro, Vicente Peg, José Jimenez, Rocio Vicario, Fabiola Cecchi, William Hoos, Jon Burrows, Todd Hembrough, Juan Carles Ferreres, José Perez-Garcia, Joaquin Arribas, Javier Cortes, Maurizio Scaltriti

Department of Morphological Sciences

Research output: Contribution to journal › Article › Research › peer-review

62 Citations (Scopus)

Abstract

© 2015 The Authors. 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.

Original language	English
Pages (from-to)	138-147
Journal	Molecular Oncology
Volume	10
Issue number	1
DOIs	https://doi.org/10.1016/j.molonc.2015.09.002
Publication status	Published - 1 Jan 2016

Keywords

Breast cancer
HER2
Immunohistochemistry
In situ hybridization
Mass spectrometry
Trastuzumab

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Nuciforo, P., Thyparambil, S., Aura, C., Garrido-Castro, A., Vilaro, M., Peg, V., Jimenez, J., Vicario, R., Cecchi, F., Hoos, W., Burrows, J., Hembrough, T., Ferreres, J. C., Perez-Garcia, J., Arribas, J., Cortes, J., & Scaltriti, M. (2016). High HER2 protein levels correlate with increased survival in breast cancer patients treated with anti-HER2 therapy. Molecular Oncology, 10(1), 138-147. https://doi.org/10.1016/j.molonc.2015.09.002

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title = "High HER2 protein levels correlate with increased survival in breast cancer patients treated with anti-HER2 therapy",

abstract = "{\textcopyright} 2015 The Authors. 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.",

keywords = "Breast cancer, HER2, Immunohistochemistry, In situ hybridization, Mass spectrometry, Trastuzumab",

author = "Paolo Nuciforo and Sheeno Thyparambil and Claudia Aura and Ana Garrido-Castro and Marta Vilaro and Vicente Peg and Jos{\'e} Jimenez and Rocio Vicario and Fabiola Cecchi and William Hoos and Jon Burrows and Todd Hembrough and Ferreres, {Juan Carles} and Jos{\'e} Perez-Garcia and Joaquin Arribas and Javier Cortes and Maurizio Scaltriti",

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Nuciforo, P, Thyparambil, S, Aura, C, Garrido-Castro, A, Vilaro, M, Peg, V, Jimenez, J, Vicario, R, Cecchi, F, Hoos, W, Burrows, J, Hembrough, T, Ferreres, JC, Perez-Garcia, J, Arribas, J, Cortes, J & Scaltriti, M 2016, 'High HER2 protein levels correlate with increased survival in breast cancer patients treated with anti-HER2 therapy', Molecular Oncology, vol. 10, no. 1, pp. 138-147. https://doi.org/10.1016/j.molonc.2015.09.002

TY - JOUR

T1 - High HER2 protein levels correlate with increased survival in breast cancer patients treated with anti-HER2 therapy

AU - Nuciforo, Paolo

AU - Thyparambil, Sheeno

AU - Aura, Claudia

AU - Garrido-Castro, Ana

AU - Vilaro, Marta

AU - Peg, Vicente

AU - Jimenez, José

AU - Vicario, Rocio

AU - Cecchi, Fabiola

AU - Hoos, William

AU - Burrows, Jon

AU - Hembrough, Todd

AU - Ferreres, Juan Carles

AU - Perez-Garcia, José

AU - Arribas, Joaquin

AU - Cortes, Javier

AU - Scaltriti, Maurizio

PY - 2016/1/1

Y1 - 2016/1/1

N2 - © 2015 The Authors. 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.

AB - © 2015 The Authors. 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.

KW - Breast cancer

KW - HER2

KW - Immunohistochemistry

KW - In situ hybridization

KW - Mass spectrometry

KW - Trastuzumab

U2 - https://doi.org/10.1016/j.molonc.2015.09.002

DO - https://doi.org/10.1016/j.molonc.2015.09.002

M3 - Article

SN - 1574-7891

VL - 10

SP - 138

EP - 147

JO - Molecular Oncology

JF - Molecular Oncology

IS - 1

ER -

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

Abstract

Keywords

UN SDGs

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