Abstract 7907: Genomic, immune, and clinical characterization of estrogen receptor-positive, HER2-low breast cancer: The NextGIM trial latest updates

Résumé fourni par la source

Abstract Background: Approximately 47-65% of estrogen receptor-positive (ER+)/HER2-negative breast cancers (BC), although classified as HER2-negative due to the absence of HER2 gene amplification, exhibit low levels of HER2 expression (referred to as HER2-low BC) with immunohistochemistry (IHC) 1+ or 2+ without amplification scores. More recently, an additional subclass—HER2-ultralow—has been proposed for tumors with HER2 IHC-0 and <10% tumor cell staining. Emerging evidence indicates that HER2-low and HER2-ultralow BC may represent biologically distinct entities compared with HER2-null BC. Here, the latest updates of the NextGIM trail, a retrospective, multicenter translational study designed to comprehensively characterize ER+/HER2-low BC, are presented. Methods: Primary tumor samples from patients enrolled in three randomized clinical trials (GIM2, GIM4, and GIM10) of the GIM (Gruppo Italiano Mammella) Investigator Group, underwent re-assessment of HER2 expression and tumor-infiltrating lymphocytes (TILs) in accordance with ASCO/CAP and TILs Working Group guidelines. In parallel, gene expression profiling was performed using the nCounter Breast Cancer 360 Panel on the NanoString platform. Clinical and survival data will be updated and integrated to evaluate potential prognostic markers and to investigate mechanisms of treatment resistance. Results: To date, from a total of 283 patients selected at participating centres, 208 samples were deemed suitable for molecular analyses after pathological and RNA quality/quantity assessment. HER2 expression has been re-evaluated in 179 samples. At diagnosis, HER2 classification was: 45.8% HER2-negative (IHC not specified), 26.8% HER2-0, 19.6% HER2-1+, and 7.8% HER2-2+. After pathological reassessment, the distribution shifted to 58.7% HER2-null, 20.7% HER2-ultralow, 15.1% HER2 1+, 5.0% HER2 2+, and 0.6% HER2 3+. Notably, HER2-null BC resulted more prevalent in older archival samples (before 2011). TILs levels ≤1% were more frequently observed in HER2-null and HER2-ultralow tumors compared with HER2-1+ and HER2-2+ (59.1% & 67.6% vs. 25.9% & 55.6%).. Genomic profiling has been completed for 208 cases and data analyses are ongoing. An integrated analysis of molecular, pathological and clinical data will be conducted upon completion of the dataset. Conclusion: The results obtained so far from HER2 re-evaluation has indicated that the interval between sample collection and reassessment can affect tissue antigenicity and immunohistochemistry results, and should be considered when re-evaluating HER2 status for therapeutic purposes. Overall, the study is expected, integrating genomic, immunological, and clinical information, to validate HER2-low and -ultralow expression as prognostic/predictive biomarkers to support personalized treatment. Citation Format: Barbara Cardinali, Alice Stella, Chiara Molinelli, Marco Bruzzone, Yanina Lizet Castillo, Francesca Pitto, Barbara Massa, Simona Pigozzi, Andrea Sciutto, Giorgia Anselmi, Maria Dono, Virna Maltoni, Benedetta Conte, Giulia Buzzatti, Davide Soldato, Gaia Griguolo, Valentina Guarneri, Mario Giuliano, Caterina Marchiò, Fabio Puglisi, Lorenzo Gerratana, Francesca Poggio, Lucia Del Mastro. Genomic, immune, and clinical characterization of estrogen receptor-positive, HER2-low breast cancer: The NextGIM trial latest updates [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7907.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.