ArticleBreast cancer research and treatment2025
Changes in HER2low and HER2-ultralow status in 47 advanced breast carcinoma core biopsies, matching surgical specimens, and their distant metastases assessed by conventional light microscopy, digital pathology, and artificial intelligence.
Article in Breast cancer research and treatment, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Mechanisms of Resistance and Synergy: The Role of Tumor Microenvironment in HER2-Low Breast Cancer Therapy.Pharmaceuticals (Basel, Switzerland) · 2026Review
- AI-enhanced precision: boosting pathologist confidence in HER2 ultra-low diagnosis through intelligent re-screening.Breast cancer research : BCR · 2026Article
- Prevalence of HER2-ultralow breast cancer in South Korea: a multicenter study by reassessment of HER2-zero cases.Journal of pathology and translational medicine · 2026Article
- HER2-Low Breast Cancer at the Interface of Pathology and Technology: Toward Precision Management.Biomedicines · 2025Review
- Standardizing the pathologic assessment of HER2-(ultra)low breast cancer: insights from a national Italian project.Pathologica · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHER2-targeted therapies have improved survival in HER2-positive breast cancer, and recent data suggest potential benefits for patients with HER2-low tumors (defined as immunohistochemistry (IHC) 1 + or 2 + and, in situ hybridization (ISH)-negative). HER2-low tumors are heterogenous, spanning the hormone receptor-positive and triple-negative subtypes. Assessing HER2-low and HER2-ultralow status remains challenging, especially across specimen types.
aimsThis study aims to (1) compare HER2 assessment using conventional microscopy, digital pathology, and an artificial intelligence (AI) model, and (2) investigate changes in HER2-low status between core biopsies, surgical specimens, and metastases. MATERIALS AND
methodsIHC slides from 47 HER2-low advanced breast carcinomas were analyzed using conventional microscopy, digital pathology, and an AI model developed on Aiforia® Create. HER2 statuses were categorized as low, ultralow (score 1 + in 1-10%), and null (score 0 or 1 + in < 1% with difficult-to-interpret minimal membranous-like staining). Changes in HER2 expression across specimen types were evaluated using agreement measures and visualization tools.
resultsThe AI model identified more HER2-low and HER2-ultralow cases compared to conventional methods, improving detection accuracy. HER2 expression differed between specimen types, with metastases exhibiting increased HER2 expression compared to surgical specimens and core biopsies. Digital pathology also showed stronger membranous staining and identified more HER2 expressor tumor cells with any kind of membranous staining than microscopy.
conclusionsAI evaluation is a more sensitive method for HER2-low assessment and reveals expression changes across disease progression. These findings emphasize the need for standardized HER2 assessment to ensure accurate therapy eligibility, particularly for novel treatments like Trastuzumab-Deruxtecan.
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