Lee, Kuo-TingKuo-TingLeePOHSIANG HUANGHsu, Chih-YiChih-YiHsuLee, Yi-HsuanYi-HsuanLeeLai, Jiun-IJiun-ILaiYEN-SHEN LUChen, Hui-WenHui-WenChenChao, Ta-ChungTa-ChungChaoLiu, Chun-YuChun-YuLiuHuang, Chi-ChengChi-ChengHuangTsai, Yi-FangYi-FangTsaiTseng, Ling-MingLing-MingTsengYang, Wei-ChenWei-ChenYangHuang, Yu-TingYu-TingHuangHuang, Ching-YaChing-YaHuangLin, Yu-CiouYu-CiouLin2025-06-162025-06-162025https://scholars.lib.ntu.edu.tw/handle/123456789/730000The binary classification of human epidermal growth factor receptor 2 (HER2) as HER2-positive [immunohistochemistry (IHC) 2+/in situ hybridization (ISH)+ or 3+] or HER2-negative (IHC 0, 1+, or 2+/ISH-) has been reassessed due to the efficacy of an anti-HER2 antibody-drug conjugate-Trastuzumab Deruxtecan in HER2-low (IHC 1+ or 2+/ISH-) unresectable/metastatic breast cancer (mBC) patients. However, little is known about the prevalence and outcomes of HER2-low mBC in Taiwan.This retrospective study rescored archived HER2 IHC slides of HER2-negative unresectable/mBC patients diagnosed from 2017 to 2020. The HER2-low prevalence (among HER2-negative), clinicopathological characteristics, treatments, and outcomes of HER2-low unresectable/mBC patients were investigated.Of the rescored HER2-negative cohort, HER2-low prevalence was 61.2 % (186/304) and slightly higher in slides tested by non-Ventana 4B5 assays (vs. Ventana 4B5) and slides from metastatic sites (vs. primary tumors). The overall percentage agreement between historical and rescored IHC was high (90.1 %). For HR+/HER2-low patients, endocrine therapies were frequently used in the first two lines of treatment, while chemotherapy was more common after the second-line treatment. Chemotherapy was the predominant treatment for HR-/HER2-low patients. Time to next treatment (TTNT) and overall survival (OS) since the first-line systemic therapy were longer in the HR+/HER2-low (N = 138) compared to HR-/HER2-low (N = 48) cohorts (median TTNT: 7.6 vs. 4.8 months; median OS: 37.7 vs. 18.8 months).This study suggested that two-thirds of HER2-negative unresectable/mBC patients in Taiwan were HER2-low. Reassessing the HER2 status of HER2-negative patients could improve treatment strategies with the evolving HER2 classification paradigm.enHer2-lowMetastatic breast cancerPrevalenceReal-world evidenceRescoreRetrospectiveTaiwan[SDGs]SDG3journal article10.1016/j.ctarc.2025.10089340139140