Evolving concepts in HER2-low breast cancer: Genomic insights, definitions, and treatment paradigms

Human epidermal growth factor receptor 2 (HER2)-low breast cancer has recently emerged as a new clinical subtype of breast cancer, benefiting from treatment with novel anti-HER2 antibody-drug conjugates. Emergence of HER2-low as a clinical subtype has raised several important questions related to the (i) biology and prognostic significance of HER2-low breast cancer, (ii) definition of HER2-low breast cancer, and (iii) clinical management of HER2-low breast cancer within existing treatment paradigms. Previously, our group evaluated the genomic landscape and prognostic significance of HER2-low using circulating tumor DNA in patients with metastatic breast cancer, determining that HER2-low did not represent a unique biologic subtype. In this review, we discuss our findings in the context of existing literature on HER2-low breast cancer and propose how best to translate current evidence into clinical management of HER2-low breast cancer.