High HER2 protein levels correlate with increased survival in breast cancer patients treated with anti-HER2 therapy
Nuciforo, Paolo (Vall d'Hebron Institut d'Oncologia)
Thyparambil, Sheeno (OncoPlex Diagnostics. USA)
Aura, Claudia (Vall d'Hebron Institut d'Oncologia)
Garrido-Castro, Ana (Hospital Universitari Vall d'Hebron)
Vilaro, Marta (Vall d'Hebron Institut d'Oncologia)
Peg, Vicente (Hospital Universitari Vall d'Hebron)
Jimenez, José (Vall d'Hebron Institut d'Oncologia)
Vicario, Rocío (Vall d'Hebron Institut d'Oncologia)
Cecchi, Fabiola (OncoPlex Diagnostics. USA)
Hoos, William (OncoPlex Diagnostics. USA)
Burrows, Jon (OncoPlex Diagnostics. USA)
Hembrough, Todd (OncoPlex Diagnostics. USA)
Ferreres Piñas, Joan Carles (Hospital Universitari Vall d'Hebron)
Pérez-Garcia, José (Hospital Universitari Vall d'Hebron)
Arribas, Joaquín V. (Vicente) (Institució Catalana de Recerca i Estudis Avançats)
Cortés, Javier (Hospital Universitari Vall d'Hebron)
Scaltriti, Maurizio (Memorial Sloan Kettering Cancer Center)
Universitat Autònoma de Barcelona

Fecha:	2016
Resumen:	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.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Breast cancer ; HER2 ; Mass spectrometry ; Trastuzumab ; Immunohistochemistry ; In situ hybridization
Publicado en:	Molecular Oncology, Vol. 10, núm 1 (January 2016) , p. 138-147, ISSN 1878-0261

DOI: 10.1016/j.molonc.2015.09.002
PMID: 26422389

10 p, 1.9 MB

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