Clinical presentations and prognostication of HER2-low and HER2-zero early breast cancer in Taiwan

Human epidermal growth factor receptor II (HER2)-low breast cancer has emerged as a clinically relevant subset of HER2-negative disease, but its prognostic significance in early-stage, real-world populations remains uncertain. We aimed to compare clinicopathological features and outcomes of HER2-low vs HER2-zero early breast cancers using a nationwide registry and to clarify the impact of hormone receptor (HR) status.

We conducted a retrospective cohort study using the Taiwan Cancer Registry (2011-2020). Eligible cases were stages 0 to III HER2-negative breast cancers managed with upfront surgery. We compared clinical characteristics , overall survival (OS) and relapse-free survival (RFS). All analyses were stratified by HR (positive vs negative) and by pathological stage.

We analyzed 38 773 patients; 65.4% were HER2-low and 34.6% were HER2-zero. HER2-low tumors were diagnosed at a slightly younger age (median 56.3 vs 57.1 years; p < 0.001) and were more often HR-positive. Across HR- and stage-defined strata, pathological stage and HR status remained the principal determinants of prognosis. Compared with HER2-zero, HER2-low showed modestly higher hazards, with small but consistent separations in OS (91.8%, 93%, 83.3%, and 86.2% for HR-positive/HER2-low, HR-positive/HER2-zero, HR-negative/HER2-low, and HR-negative/HER2-zero breast cancers; p < 0.0001) and RFS (95.6%, 97.1%, 89.6%, and 91.1% for HR-positive/HER2-low, HR-positive/HER2-zero, HR-negative/HER2-low, and HR-negative/HER2-zero breast cancers; p < 0.0001) within strata, with the exception of stage 0.

In Taiwanese early-stage breast cancer, HER2-low is common and associated with greater HR positivity and modestly inferior OS/RFS relative to HER2-zero after HR and stage stratification. Further studies are warranted to understand the biological and therapeutic relevance of this newly established taxonomy.