Prevalence and concordance of HER2-low and HER2-ultralow status between historical and rescored results in a multicentre study of breast cancer patients in China

Abstract Background Accurately assessing HER2-low (immunohistochemistry [IHC] 1 + and IHC 2+/in situ hybridization [ISH]–) and HER2-ultralow (IHC > 0 < 1+) is essential given the emergence of novel therapies. Thorough understanding of the reproducibility of rescoring IHC stained slides or re-s...

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Main Authors: Hong Lv, Junqiu Yue, Qingfu Zhang, Fangping Xu, Peng Gao, Haifeng Yang, Xiu Nie, Lingfei Kong, Guanjun Zhang, Jianming Li, Shiwei Xiao, Hongmei Wu, Aiyan Xing, Min Hong, Jun Fan, Huijuan Guan, Peilong Cao, Hengli Ni, Wentao Yang
Format: Article
Language:English
Published: BMC 2025-03-01
Series:Breast Cancer Research
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Online Access:https://doi.org/10.1186/s13058-025-02001-0
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author Hong Lv
Junqiu Yue
Qingfu Zhang
Fangping Xu
Peng Gao
Haifeng Yang
Xiu Nie
Lingfei Kong
Guanjun Zhang
Jianming Li
Shiwei Xiao
Hongmei Wu
Aiyan Xing
Min Hong
Jun Fan
Huijuan Guan
Peilong Cao
Hengli Ni
Wentao Yang
author_facet Hong Lv
Junqiu Yue
Qingfu Zhang
Fangping Xu
Peng Gao
Haifeng Yang
Xiu Nie
Lingfei Kong
Guanjun Zhang
Jianming Li
Shiwei Xiao
Hongmei Wu
Aiyan Xing
Min Hong
Jun Fan
Huijuan Guan
Peilong Cao
Hengli Ni
Wentao Yang
author_sort Hong Lv
collection DOAJ
description Abstract Background Accurately assessing HER2-low (immunohistochemistry [IHC] 1 + and IHC 2+/in situ hybridization [ISH]–) and HER2-ultralow (IHC > 0 < 1+) is essential given the emergence of novel therapies. Thorough understanding of the reproducibility of rescoring IHC stained slides or re-staining archived tissue slides is essential. Methods 2,869 breast cancer patients diagnosed between July 2021 and July 2022 from 10 hospitals in China were included in this multicentre study. The prevalence of different HER2 expression levels and distribution of HER2 IHC scores were assessed by HER2 status determination from rescored historical slides. Concordance was evaluated across historical results versus rescored results, historical results versus re-stained results, and leading center results versus local site results. Clinicopathological characteristics were retrospectively analyzed as well. Results HER2 IHC 0, IHC 1+, IHC 2+, and IHC 3 + were identified in 682 (23.8%), 871 (30.4%), 801 (27.9%), and 515 (18.0%) cases, respectively. HER2-positive, HER2-low, and HER2 IHC 0 (HER2-ultralow and IHC null) were identified in 21.7%, 54.5%, and 23.8% of cases, respectively. The prevalence of HER2-ultralow and IHC null was 10.6% and 13.2%, respectively. The concordance for HER2-ultralow was 43.3%; 30% of cases that were scored as HER2-ultralow at local sites were rescored as HER2-null and 26.7% of cases were rescored as IHC 1 + at the leading site. Overall, there was substantial agreement (83.1%) between rescored and historical IHC results. A high concordance rate of 91.7% was observed for HER2-low classification. Conclusions This is the first multicenter study to determine the prevalence of HER2-low and HER2-ultralow based on rescored results in the Chinese breast cancer population. The concordance analysis carries important implications for the diagnosis of HER2-low and HER2-ultralow cases in clinical practice. The relatively low concordance in identifying HER2-ultralow suggested that the reproducibility of scoring HER2-ultralow needed to be improved through training. Trial registration ClinicalTrials.gov identifier NCT05203458.
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spelling doaj-art-63dcf44c6fb1424f9dd94f131d4d34e72025-08-20T02:10:15ZengBMCBreast Cancer Research1465-542X2025-03-0127111110.1186/s13058-025-02001-0Prevalence and concordance of HER2-low and HER2-ultralow status between historical and rescored results in a multicentre study of breast cancer patients in ChinaHong Lv0Junqiu Yue1Qingfu Zhang2Fangping Xu3Peng Gao4Haifeng Yang5Xiu Nie6Lingfei Kong7Guanjun Zhang8Jianming Li9Shiwei Xiao10Hongmei Wu11Aiyan Xing12Min Hong13Jun Fan14Huijuan Guan15Peilong Cao16Hengli Ni17Wentao Yang18Department of Pathology, Fudan University Shanghai Cancer CenterDepartment of Pathology, Hubei Cancer HospitalDepartment of Pathology, The First Hospital of China Medical UniversityDepartment of Pathology, Guangdong Provincial People’s HospitalDepartment of Pathology, Qilu Hospital of Shandong UniversityDepartment of Pathology, Guangdong Provincial Hospital of Chinese MedicineDepartment of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Pathology, Henan Provincial People’s HospitalDepartment of Pathology, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Pathology, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityDepartment of Pathology, Hubei Cancer HospitalDepartment of Pathology, Guangdong Provincial People’s HospitalDepartment of Pathology, Qilu Hospital of Shandong UniversityDepartment of Pathology, Guangdong Provincial Hospital of Chinese MedicineDepartment of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Pathology, Henan Provincial People’s HospitalDepartment of Pathology, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Pathology, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityDepartment of Pathology, Fudan University Shanghai Cancer CenterAbstract Background Accurately assessing HER2-low (immunohistochemistry [IHC] 1 + and IHC 2+/in situ hybridization [ISH]–) and HER2-ultralow (IHC > 0 < 1+) is essential given the emergence of novel therapies. Thorough understanding of the reproducibility of rescoring IHC stained slides or re-staining archived tissue slides is essential. Methods 2,869 breast cancer patients diagnosed between July 2021 and July 2022 from 10 hospitals in China were included in this multicentre study. The prevalence of different HER2 expression levels and distribution of HER2 IHC scores were assessed by HER2 status determination from rescored historical slides. Concordance was evaluated across historical results versus rescored results, historical results versus re-stained results, and leading center results versus local site results. Clinicopathological characteristics were retrospectively analyzed as well. Results HER2 IHC 0, IHC 1+, IHC 2+, and IHC 3 + were identified in 682 (23.8%), 871 (30.4%), 801 (27.9%), and 515 (18.0%) cases, respectively. HER2-positive, HER2-low, and HER2 IHC 0 (HER2-ultralow and IHC null) were identified in 21.7%, 54.5%, and 23.8% of cases, respectively. The prevalence of HER2-ultralow and IHC null was 10.6% and 13.2%, respectively. The concordance for HER2-ultralow was 43.3%; 30% of cases that were scored as HER2-ultralow at local sites were rescored as HER2-null and 26.7% of cases were rescored as IHC 1 + at the leading site. Overall, there was substantial agreement (83.1%) between rescored and historical IHC results. A high concordance rate of 91.7% was observed for HER2-low classification. Conclusions This is the first multicenter study to determine the prevalence of HER2-low and HER2-ultralow based on rescored results in the Chinese breast cancer population. The concordance analysis carries important implications for the diagnosis of HER2-low and HER2-ultralow cases in clinical practice. The relatively low concordance in identifying HER2-ultralow suggested that the reproducibility of scoring HER2-ultralow needed to be improved through training. Trial registration ClinicalTrials.gov identifier NCT05203458.https://doi.org/10.1186/s13058-025-02001-0Breast cancerConcordance, HER2-lowHER2-ultralowPrevalence
spellingShingle Hong Lv
Junqiu Yue
Qingfu Zhang
Fangping Xu
Peng Gao
Haifeng Yang
Xiu Nie
Lingfei Kong
Guanjun Zhang
Jianming Li
Shiwei Xiao
Hongmei Wu
Aiyan Xing
Min Hong
Jun Fan
Huijuan Guan
Peilong Cao
Hengli Ni
Wentao Yang
Prevalence and concordance of HER2-low and HER2-ultralow status between historical and rescored results in a multicentre study of breast cancer patients in China
Breast Cancer Research
Breast cancer
Concordance, HER2-low
HER2-ultralow
Prevalence
title Prevalence and concordance of HER2-low and HER2-ultralow status between historical and rescored results in a multicentre study of breast cancer patients in China
title_full Prevalence and concordance of HER2-low and HER2-ultralow status between historical and rescored results in a multicentre study of breast cancer patients in China
title_fullStr Prevalence and concordance of HER2-low and HER2-ultralow status between historical and rescored results in a multicentre study of breast cancer patients in China
title_full_unstemmed Prevalence and concordance of HER2-low and HER2-ultralow status between historical and rescored results in a multicentre study of breast cancer patients in China
title_short Prevalence and concordance of HER2-low and HER2-ultralow status between historical and rescored results in a multicentre study of breast cancer patients in China
title_sort prevalence and concordance of her2 low and her2 ultralow status between historical and rescored results in a multicentre study of breast cancer patients in china
topic Breast cancer
Concordance, HER2-low
HER2-ultralow
Prevalence
url https://doi.org/10.1186/s13058-025-02001-0
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