ORIGINAL ARTICLE
Figure from article: HER2-low breast cancer:...
 
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ABSTRACT
The introduction of antibody-drug conjugates, particularly trastuzumab deruxtecan, has fundamentally changed the clinical significance of low HER2 expression in breast cancer. Consequently, accurate discrimination between human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) score 0 and HER2-low (IHC 1+ or IHC 2+/ISH-negative) has become increasingly important in routine pathological practice. This retrospective single-center observational study included consecutive patients diagnosed with invasive breast carcinoma between January 2023 and December 2024. Histopathological and immunohistochemical slides were re-evaluated according to current American Society of Clinical Oncology/College of American Pathologists recommendations. Cases were reclassified into HER2 0, HER2-low, and HER2-positive categories. Clinicopathological variables, including patient age, histological subtype, hormone receptor status, Ki-67 proliferation index, histological grade, and biological subtype, were analyzed using descriptive statistics. Seventy-eight patients were analysed. Following reassessment, HER2-low tumors accounted for 33.3% (26/78) of all invasive breast cancers. Fifteen tumors initially classified as HER2 0 were reclassified as HER2-low. All HER2-low tumors were invasive carcinoma of no special type. Luminal B represented the predominant molecular subtype (65.4%), followed by triple-negative breast cancer (30.8%) and luminal A tumors (3.8%). Estrogen receptor expression was observed in 69.2% of HER2-low tumors, while progesterone receptor expression was detected in 61.5%. Reclassification of HER2 expression substantially increased the number of patients classified as HER2-low, emphasizing the importance of precise immunohistochemical assessment, particularly in distinguishing IHC score 0 from IHC score 1+. These findings highlight the growing clinical relevance of standardized HER2 assessment in identifying patients who may become eligible for HER2-targeted antibody-drug conjugate therapy.
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