Illuminating the clinicopathological and genomic landscape of HER2-null, ultralow, and low breast cancers: insights into diagnostic discordance between biopsy and surgical excision

This study aimed to evaluate the representativeness of HER2-low and ultralow status in core needle biopsies (CNB) with AI assistance and investigate the clinicopathological and molecular characteristics of HER2-ultralow, HER2-null, and HER2-low breast cancer patients in the Chinese population. CNB-surgical excision biopsy (SEB) concordance was high between HER2-null and ultralow/low groups but limited in the ultralow subgroup. Univariate analyses showed that TNBC subtype, HR negative expression, high Ki-67 index, and AR negative expression were potential indicative factors for the discordance of HER2 status between CNB and SEB. Clinicopathological features showed no significant differences between low and ultralow groups. Genomic analysis revealed subtle mutation pattern differences. The HER2 copy number level did not show additional value in distinguishing subgroups. Conclusions highlight the need to address CNB-SEB diagnostic discordance, particularly in ultralow cases, emphasizing the necessity of HER2 retesting in surgical specimens.