Comparing digital and glass slide methods for determining the HER2-low and negative categories in breast cancer.

person Xuemin Xue Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China info_outline Xuemin Xue, Changyuan Guo, Yun Ling, Rujing Jia, Wenting Huang, Yanfeng Xi, Jianming Ying

Authors person Xuemin Xue Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China info_outline Xuemin Xue, Changyuan Guo, Yun Ling, Rujing Jia, Wenting Huang, Yanfeng Xi, Jianming Ying Organizations Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, Pathology Department, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, Special Standard Laboratory Accreditation Department, China National Accreditation Service for Conformity Assessment, Beijing, China, Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China, Department of Pathology, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China Abstract Disclosures Research Funding Other the National Anti-Tumor Drug Surveillance System of National Cancer Center Background: The promising clinical use of anti-HER2 antibody–drug conjugates (ADCs) in patients with immunohistochemistry (IHC)-based HER2-Low (1+, and 2+/FISH−) breast cancer has been discovered recently. Thus, pathologists and clinicians are now under increasing pressure to discriminate HER2-low from HER2-0. Methods: This multi-institutional retrospective breast cancer study selected 60 cases of paired digital and glass slides with HER2-Low (IHC 1+, and 2+/FISH−) and HER2-0 according to the original pathology reports, including 20 cases per staining intensity. These cases were re-evaluated by 37 pathologists from three hospitals. After excluding those cases with HER2 ≥ 2+ confirmed by both digital and glass slides with ≥ 85% agreement across 37 pathologists, the remaining cases were reclassified into “HER2-Neg” and “HER2-Low” categories with ≥ 85% agreement. If a slide could not be placed into one of these two categories, it will be labeled “HER2-Ambiguous”. Results: After excluding 13 cases with HER2 ≥ 2+ confirmed by both digital and glass slides with ≥ 85% agreement, the remaining 47 cases were reclassified into “HER2-Neg”, “HER2-Ambiguous” and “HER2-Low” categories. Therefore, the Kappa value for these three categories between the digital and glass slides was 0.597 (p = 2.50e-07). Interestingly, our study demonstrated that a significantly higher proportion of HER2-Low cases were identified on digital slides (48.9%, 23/47) than on glass slides (38.3%, 18/47; BhapkarTest, p = 3.17e-04). Five of the twelve (41.7%) HER2-Ambiguous cases diagnosed using glass slides were reclassified as HER2-Low using digital slides. Conclusions: Our study indicated that, compared to glass slides, digital slides may tend to shift HER2-0 to HER2-low category, potentially increasing breast cancer patients access to anti-HER2 ADCs, although the clinical benefit and biological characteristics have not been fully investigated. Thus, further investigation is warranted.