ArticleThe oncologist2025
Exploring immune activation patterns in HER2-low and HER2-ultralow breast cancer subtypes.
Article in The oncologist, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Antibody-Drug Conjugates Targeting HER2 and Trop-2: A New Force in Precision Treatment for Solid Tumors.Pharmaceuticals (Basel, Switzerland) · 2026Review
- HER2 assessment in urothelial carcinoma: standardization challenges and the path forward.Cancer metastasis reviews · 2026Review
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3 authors.
Funding
Abstract
backgroundA deeper understanding of the molecular and clinical characteristics of HER2-low and ultralow breast cancer (BC) subtypes is essential for advancing therapeutic strategies.
methodsThree independent GEO datasets with microarray and IHC/FISH data from 510 BC patients were analyzed to establish reliable HER2 expression cutoff values (>3034 for HER2-positivity and <1780 for HER2-ultralow), defining HER2-positive (HER2+), HER2-low, and HER2-ultralow cohorts. Combined with hormone receptor status, six distinct BC subgroups were identified. Prognosis was evaluated using univariate and multivariate survival analysis in a dataset of 7830 BC patients, alongside correlative analysis of 17 immune-related gene signatures across subgroups. A PubMed literature review compared our findings with existing studies.
resultsIn hormone receptor-positive (HR+) patients, HER2-low tumors were associated with better prognosis than HER2-ultralow and HER2+ subgroups (P = .0048 for relapse-free survival (RFS) and P = .0015 for distant-metastasis-free survival (DMFS)). No prognostic significance was observed in HR-negative (HR-) patients. Immune gene activation was consistently higher in HR- tumors, with HER2-low (HR+ and HR-) and HR-/HER2+ patients showing significant immune signature overlap. While HR+/HER2-ultralow and HR+/HER2+ patients had modest immune activation, HR-/HER2-ultralow patients exhibited the strongest association with immune signaling, including IFN signaling, T cell-activating cytokines, and cytotoxic effector molecules.
conclusionsThese findings, supported by a comprehensive literature review, indicate that patients with HER2-low and HER2-ultralow BC exhibit distinct immune patterns, which supports their classification as unique BC subgroups.
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