Genomic and clinical characterization of estrogen receptor–positive/HER2-negative early breast cancer: Results from the NextGIM study.

Résumé fourni par la source

e12590 Background: Estrogen Receptor–Positive (ER+)/HER2-Negative early breast cancer (BC) is biologically heterogeneous: while most patients experience a favourable prognosis, 15–30% still relapse despite standard adjuvant therapy. As therapeutic options expand, reliable biomarkers are needed to guide escalation and de-escalation strategies. Genomic signatures and low HER2 expression have emerged as potential tools for refining prognosis and predicting treatment benefit, although their roles beyond specific therapeutic contexts remain uncertain. Methods: NextGIM is a multicenter retrospective translational study integrating clinicopathologic and molecular data from patients with ER+/HER2-negative early BC enrolled in the GIM2, GIM4, and GIM10 trials. Reassessment of tumor-infiltrating lymphocytes (TILs) and HER2 expression was performed, and associations with invasive disease-free survival (iDFS) and overall survival (OS) were evaluated. Comprehensive gene expression profiling was performed using the nCounter BC 360 panel platform. Results: Overall, 272 patients were included: median age was 60 years (IQR 53–67), and 203 (74.6%) underwent surgery before 2011. Most tumors were T1 (163, 59.9%), and nearly half of patients had N1 disease (128, 47.1%). At diagnosis, HER2 reporting reflected trial-era pathology, with 106 (39.0%) tumors classified as HER2-negative without a documented immunohistochemistry (IHC) score, 77 (28.3%) as HER2-zero, 52 (19.1%) as HER2 1+, and 37 (13.6%) as HER2 2+ without ISH amplification. Among the 225 samples already reassessed, 126 (56.0%) were classified as HER2-null, 37 (16.4%) as HER2-ultralow, 43 (19.1%) as HER2 1+, 18 (8.0%) as HER2 2+, and 1 (0.4%) as HER2 3+. Most HER2-null BC were diagnosed before 2011 (76.2%), whereas HER2-ultralow BC displayed a more even distribution (54.1% before vs. 45.9% after 2011; p = 0.050). TILs ≤1% were observed in 55.6% of HER2-null BC, 67.6% of HER2-ultralow cases, 34.9% of HER2 1+ tumors, and 27.8% of HER2 2+ BC. After a median follow-up of 20.3 years (IQR 10.1–21.8), iDFS and OS did not differ across HER2 subgroups defined by reassessment (iDFS: p = 0.385; OS: p = 0.792). Preliminary gene expression data from 123 samples showed a progressive increase in ERBB2 expression with rising HER2 scores, accompanied by only modest variation in proliferation-related genes (e.g., AURKA, FGFR4, MKI67, CCNA2, CDK1, CDKN3). Conclusions: The predominance of HER2-null cases among older specimens suggests a potential contribution of pre-analytical and storage-related factors, which may limit the reliability of HER2 IHC reassessment in archival tissue. Repeat testing on a recent specimen should be considered when HER2 status is re-evaluated to inform treatment decisions.

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