Abstract PS4-01-20: Clinico-pathological and genomic features of HER2-low early Breast Cancer (eBC). Results of retrospective analysis of seven adjuvant trials by the Hellenic Cooperative Oncology Group (HeCOG)

Abstract Background: HER2-low breast cancers are a mixture of luminal and triple negative tumors. Precise molecular characterization can help refine treatment strategies with novel antibody-drug conjugates and improve outcomes in this patient subgroup. Methods: We used central ER/PgR (HR) and HER2/ERBB2 IHC/FISH assessment to define HER2-low (IHC 1+ or 2+/FISH non-amplified), HER2-zero (IHC 0) and Luminal A/ Luminal B/ TNBC subtypes across 7 prospective adjuvant studies in which eBC patients were treated with dose dense sequential chemotherapy. Retrospective analysis of clinico-pathological data and IHC markers from tissue microarray cores was performed on N=2,751 cases, whereas DNA next generation sequencing (NGS) data were available in a subset of N=1,120 tumors. Heterogeneity was investigated by comparing HER2-low concordant (HER2-low_c) cases, when all cores were scored consistently as HER2-low (>0) and HER2-low discordant (HER2-low_d) cases, when at least one core was scored “0”. Results: First, HER2-low tumors were more likely to be HR + (p