Abstract
INTRODUCTION: HER2-negative breast cancers can be further subclassified into HER2-low and HER2-zero subtypes. The DESTINY-Breast04 trial has established HER2-low as a research hotspot, with recent studies indicating superior survival rates in HER2-low patients than HER2-zero patients. The impact of heterogeneous hormone receptor (HR) expression patterns on HER2-negative breast cancer has not been comprehensively investigated. This study explored how varying ER and PR expression patterns affect survival rates in patients with HER2-negative breast cancer. METHODS: This retrospective study comprised 648 HER2-negative breast cancer patients treated at our hospital between 2010 and 2023. Six subgroups were compared, including ER+/PR+/HER2-low, ER+/PR+/HER2-zero, single HR+/HER2-low, single HR/HER2-zero, ER-/PR-/HER2-low, and ER-/PR-/HER2-zero. RESULT: With disease-free survival and overall survival as primary endpoints, the cohort included 648 HER2-negative breast cancer patients. Compared to HER2-zero, HER2-low patients showed a higher proportion of ER positivity (q = 0.016). The ER+/PR + group exhibited a higher proportion of HER2-low, lower N stage, lower histological grade, and lower Ki-67% (p < 0.001), and were also more likely to achieve pCR after neoadjuvant therapy. In the overall population, HER2-low exhibited better survival outcomes. Compared to single HR+/HER2-low, ER+/PR+/HER2-low had longer DFS (p < 0.001). HER2-low is an independent prognostic factor for survival outcomes in HER2-negative patients. CONCLUSION: Our findings suggest that HER2-low breast cancer is associated with improved survival outcomes compared to HER2-zero breast cancer. HER2-low breast cancer exhibits different survival outcomes across different HR subgroups. These findings may guide future biomarker-driven treatment strategies in HER2-negative breast cancer.