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Background: HER2 antibody-drug conjugates are reshaping the conventional HER2 status dichotomy, heightening expectations in the realm of HER2 status assessment and its associated molecular characterization. In this context, we have tasked gene expression profiling (GEP) with accurately identifying HER2-low tumors and exploring variations in tumor-infiltrating immune cell (TIIC) composition according to HER2-low GEP-based scores.

Materials and Methods: GEP data from primary tumors of newly diagnosed breast cancer patients (n= 304) were collected from institutional databases INT1 (n= 125), INT2 (n= 84), and INT3 (n= 95), and used for the generation of a specific HER2-low signature and for the deconvolution of TIICs by CIBERSORTx. The association between HER2-low signature scores and TIICs was analysed using Spearman correlation coefficient (r), with a 95% confidence interval (CI) calculated …