Prognostic Impact of HER2-Low and HER2-Zero in Resectable Breast Cancer with Different Hormone Receptor Status: A Landmark Analysis of Real-World Data from the National Cancer Center of China

Background The prognostic impact of HER2-low on overall survival (OS) and disease-free survival (DFS) in patients with resectable breast cancer (BC) remains controversial, partly resulting from the hormone receptor (HR) status. Objective To investigate the prognostic impact of HER2-low in different HR subgroups. Patients and Methods We retrospectively retrieved medical records of treatment-naive primary HER2-low and HER2-zero BC patients who were diagnosed with invasive ductal carcinoma and underwent surgery in the Cancer Hospital of the Chinese Academy of Medical Sciences from January 2009 to September 2017 ( n = 7371). We compared the clinicopathologic features and performed Cox regression and landmark survival analyses to explore the prognostic impact of HER2-low on survival outcomes during distinct post-surgery intervals—36 months, 60 months, and 120 months. Results HER2-low BC, compared to HER2-zero BC, exhibited less aggressive clinicopathologic features, such as smaller invasion size, lower grade, increased nerve invasion, higher HR positivity, and a higher proportion of low-Ki67 cases. In the HR-positive subgroup, HER2-low demonstrated improved OS ( p = 0.046) and DFS ( p = 0.026) within 60 months. Conversely, HER2-low displayed worse DFS ( p = 0.046) in the HR-negative subgroup after 36 months from surgery. The findings remained robust in uni- and multi-variable Cox models. Conclusions HER2-low BCs manifested less aggressive clinicopathologic features than the HER2-zero cases. The prognostic impact of HER2-low in resectable BCs exhibits variability contingent upon the patients’ HR status.