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Original Article
- HER2-low and ultralow breast cancer: interobserver challenges and lessons from a consensus study
- Jiwon Koh, Yoon Jin Cha, Eun Yoon Cho, Ahwon Lee, Ja Seung Koo, So Yeon Park, Min Hwan Kim, Jae Ho Jeong, Gyungyub Gong
- Received December 17, 2025 Accepted January 8, 2026 Published online March 20, 2026
- DOI: https://doi.org/10.4132/jptm.2026.01.08 [Epub ahead of print]
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Abstract
PDF - Background
The recent approval of trastuzumab deruxtecan for human epidermal growth factor receptor 2 (HER2)–low and HER2-ultralow breast cancer mandates an adequate assessment of these categories. Methods: Seven breast pathologists from the Breast Pathology Study Group of the Korean Society of Pathologists held an on-site expert consensus meeting. Fifteen sets of virtual whole slide images (WSI) of hematoxylin and eosin stain and HER2 immunohistochemistry were provided. The pathologists were given 60 minutes to submit their diagnosis of HER2 expression into null, ultralow, 1+, 2+, or 3+. Afterwards, in-depth discussion and consensus diagnoses were made by real-time visualization of the WSI. Results: After the consensus meeting, unanimous 100% agreements were seen only in five (33.3%) of the examined cases, which consisted of three 1+ cases and two 2+ cases. Two cases (13.3%) had mild disagreement, with only one pathologist’s disagreement. Of note, eight cases (53.3%) showed significant disagreement, defined by more than two pathologists’ disagreement. All HER2-null cases were reclassified as ultralow after consensus review, suggesting potential widespread underclassification of ultralow cases in clinical practice. Conclusions: Experts had significant discrepancies in interpreting HER2-low/ultralow status. It is important to assess if the distinction between HER2-low and ultralow is strictly required and if HER2-null breast cancer exists in reality.
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