Clinicopathological and prognostic comparative study of HER2-low versus HER2-zero breast cancer

Background: Breast cancer is a biologically diverse disease and recent advancements further highlight the significance of the level of HER2 expression for determining prognosis and therapy. While HER2-positive tumors respond significantly to targeted anti-HER2 therapy, the novel emerging subgroup of HER2-low breast cancer, defined by immunohistochemistry expression 1+ or 2+ with negative for gene amplification on in-situ hybridization has shown good results following the treatment by antibody-drug conjugates (ADCs) like trastuzumab deruxtecan. However, there remains limited comparative data on HER2-low versus HER2-zero breast cancers. Objective: To compare the clinicopathological features and disease-free survival outcomes between HER2-low and HER2-zero breast cancer patients and to assess their prognostic differences, especially in relation to hormone receptor (HR) status. Methods: A retrospective, single-center study was done at Kailash Cancer Hospital and Research Centre, Gujarat, involving 783 HER2-negative breast cancer patients who were subjected to surgical and systemic interventions between January 2016 and December 2023. This cohort was further subdivided into tumors with low HER2 expression (N=329) and tumors with absent/ zero HER2 expression (N=454) groups analyzed over IHC and ISH results. Clinicopathological data, treatment details and disease-free survival outcomes were interpretated using chi-square tests, Kaplan-Meier survival curves, and Cox proportional hazards regression models. Results: In this study, HER2-low tumors were found to be frequently positive for hormone receptor expression (ER &/ PR) (81.76% in HER2 low and 67.62% in HER2 zero, p