HER2 expression in a molecularly defined cohort of endometrial cancer patients: The SPECTRUM study

作者：Alfonso Cortés-Salgado, Esther Moreno-Moreno, Irene Carretero‐Barrio, Tamara Caniego-Casas, Eva Cristóbal, Laura del Campo-Albendea, Eva Guerra, Víctor Alía, P. Pérez de Aguado, Virginia Corraliza, JOSE M. PALACIOS, Belén Perez‐Mies · 发表于：Gynecologic Oncology · 年份：2025 · DOI：10.1016/j.ygyno.2025.02.005 · 被引用次数：12 · 研究领域：HER2/EGFR in Cancer Research、Endometrial and Cervical Cancer Treatments、Estrogen and related hormone effects

BACKGROUND: HER2 antibody-drug conjugates like Trastuzumab deruxtecan (TDxd) have shown efficacy in HER2-low cancers, however the prevalence and clinical impact of HER2-low in endometrial cancer (EC) remains unclear. This study investigates HER2 expression in EC, focusing on HER2-low frequency, its distribution across histologic and molecular subtypes, intratumoral heterogeneity, and prognostic significance. METHODS: This retrospective analysis included EC patients categorized histologically and molecularly, using ASCO/CAP HER2 scoring guidelines for endometrial, gastric, and breast cancers. The main aim was to determine HER2-low frequency by molecular subtype, with secondary goals of assessing HER2 heterogeneity, changes between primary and recurrent tumors, guidelines concordance and the impact of HER2 status on recurrence-free (RFS) and overall survival (OS). RESULTS: 193 EC patients were included, 111 low grade endometrioid EC and 82 high grade EC with various histotypes. Based on endometrial criteria, 69.9 % were HER2-negative, 25.8 % HER2-low, and 4.3 % HER2-positive, with HER2-low being most common in POLEmut (66.7 %) and p53abn (45.1 %) subtypes. Low heterogeneity in HER2 expression was observed between different tumors areas and between primary tumors and their recurrences. The endometrial and gastric criteria had high concordance (88.7 %), with endometrial guidelines detecting more HER2-low cases. Neither HER2-low nor HER2-positivity versus HER2-negativity had an im...