Clinical Outcomes in Early-Stage HER2-Low and HER2-Zero Breast Cancer: Single-Center Experience

<b>Background/Objectives:</b> The goal of this study is to characterize the survival patterns and outcomes of women with early-stage breast cancer, with a particular emphasis on the distinction between HER2-low and HER2-zero expression. There is limited real-world data on how patients with HER2-negative or HER2-low metastatic or recurrent breast cancer are treated. <b>Methods:</b> We retrospectively analyzed the medical records of 1500 breast cancer patients diagnosed between January 2020 and December 2024. From this cohort, 99 patients with HER2-low and 34 patients with HER2-zero early-stage breast cancer were included in our analysis. HER2 low was defined as Immunohistochemistry (IHC) 1+ or IHC 2+ with negative Silver In situ Hybridization (SISH), while HER2 zero was defined as IHC 0. Statistical analyses, including Kaplan-Meier survival analyses and log-rank tests for group comparisons, were performed using IBM SPSS Statistics. <b>Results:</b> The median age of patients was 55 years. The HER2-zero group exhibited a higher incidence of brain, liver, bone, and lung metastases (<i>p</i> < 0.001 for all) and increased use of CDK4/6 inhibitors (<i>p</i> < 0.001). In univariate analyses, younger age, an HER2-zero status, and the absence of metastases were associated with improved disease-free survival (DFS) and overall survival (OS). However, in multivariate analyses, an HER2-zero status independently predicted longer DFS (HR = 0.14, 95% CI: 0.05-0.41, <i>p</i> < 0.001) and OS (HR = 0.16, 95% CI: 0.042-0.6, <i>p</i> = 0.007). <b>Conclusions:</b> Our study revealed distinct metastatic patterns and survival outcomes between HER2-low and HER2-zero early-stage breast cancers. Despite a higher metastatic burden in univariate analyses, HER2 zero status was independently associated with longer DFS and OS in multivariate analyses, highlighting their biological heterogeneity and the need for further research to inform tailored strategies.