We have recently described the correlation between quantitative measures of HER2 expression or HER2 homodimers by the HERmark assay and ob−jective response (RR), time−to progression (TTP), and overall survival (OS) in an ex−panded access cohort of trastuzumab−treated HER2−positive patients with metastatic breast cancer (MBC) who were stringently selected by fluorescence in situ hybri−dization (FISH). Multivariate analyses suggested a continuum of HER2 expression that correlated with outcome following trastuzumab. Here we investigate the relationship between HER2 expression or HER2 homodimers and OS in a clinic−based population of patients with MBC selected primarily by IHC.

HERmark, a proximity−based assay designed to detect and quantitate protein expression and dimerization in formalin−fixed paraffin−embedded (FFPE) tissues, was used to measure HER2 expression and HER2 homodimers in FFPE samples from patients with MBC. Assay results were correlated with OS using un−ivariate Kaplan−Meier, hazard function plots, and multivariate Cox regression analyses.

Initial analyses revealed a parabolic relationship between continuous measures of HER2 expression and risk of death, suggesting that the assumption of linearity for the HER2 expression measurements may be inappropriate in subse−quent multivariate analyses. Cox regression analyses using the categorized variable of HER2 expression level demonstrated that higher HER2 levels predicted better survival outcomes following trastuzumab treatment in the high HER2−expressing group.

These data suggest that the quantitative amount of HER2 expression measured by Hermark may be a new useful marker to identify a more relevant target population for trastuzumab treatment in patients with MBC.

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