Correlation of high levels of HER2 measured by multiplex mass spectrometry with increased overall survival in patients treated with anti-HER2-based therapy.

Abstract

649 Background: There is evidence that increased absolute levels of the HER2 receptor in breast cancer positively correlates with a clinical benefit from anti-HER2 therapies. The current method of HER2 evaluation, immunohistochemistry (IHC), does not allow for absolute HER2 quantification and is prone to false-positives. Thus, a significant portion of patients classified as HER2-positive actually express low levels of the receptor. We quantitated absolute levels of HER2 using a mass spectrometry-based assay and correlated expression levels with the anti-HER2 therapy benefit. Methods: Formalin-fixed, paraffin-embedded (FFPE) tumor sections were microdissected and proteins were solubilized and digested by trypsin in Liquid Tissue buffer. After digestion, internal standards were added and absolute quantitation for multiple proteins was performed using selected reaction monitoring (SRM) mass spectrometry. Results: 26 HER2-positive (IHC 3+) breast cancer samples from patients treated with anti-HER2 therapy wer...