Bridging practice and precision: a quantitative HER2 protein assay ready for clinical use in guiding trastuzumab deruxtecan therapy
Year: 2026
Type: article
Abstract: Purpose Current daily usage of Trastuzumab Deruxtecan (T-DXd) is guided by immunohistochemistry (IHC)-based HER2 assessment, with known inconsistency and inaccuracy to differentiating IHC 0 from 1 +. In this study, a quantitative HER2 assay based on the Quantitative Dot Blot (QDB) method was explored to fill this unmet need. Methods Consecutive resection specimens of HER2 IHC 0 and 1+ from invasive breast cancer patients were assigned to training (n=106) and validation cohorts ( n= 119), respectively by admission time. Protein lysates were extracted from 2x5 μm FFPE slices for HER2 quantification while the adjacent slice was used for IHC staining. Results QDB was demonstrated to be more consistent than IHC with an inter-rater Intraclass Correlation Coefficient (ICC) of 0.877 (95%CI: 0.840-0.908) vs. 0.513 (95%CI: 0.433-0.601). Receiver Operating Characteristic (ROC) analysis was performed benchmarked with unanimous agreement of 18 pathologists in the training cohort to achieve an Area Under the Curve (AUC) of 0.9477 (p<0.005). A cutoff of 0.2746 nmole/g was also identified with its imprecision interval to stratify specimens into 0 ( 5 ), equivocal (≥ C 5 & ≤ C 95 ) and 1+ (> C 95 ), with overall concordance of 90.9% and 87.3% when benchmarked with unanimous and consensus agreement (≥75%) of pathologists in the training cohort, and 92.0% and 90.5% when validated double-blinded with 12 pathologists in the validation cohort. More importantly, even among specimens unanimously categorized as IHC 0, there were ~15% specimens classified as 1+ by QDB. Conclusion Our results supports the QDB HER2 assay as an alternative option to guide T-DXd daily usage by distinguish Her2-low from Her2 0 while setting the stage for outcome-based patient stratification.
Source: Frontiers in Oncology
Authors: Junmei Hao, Xiaochun Fei, Fangfang Zou, Qian Hu, Linlin Du, Liya Yu, Xuanye Bai, Shasha Bi, Qinghua Cao, Weishan Chen, Qun Dai, Tingting Guo, Hai Huang, Wenwei Jiang, Baohua Li, Lixia Li, Jingjing Liu, Tong Liu, Xiaoqin Liu, Jiahong Lyu, Yue Pan, Xiaoqing Shao, Fangrong Tang, Tingting Wang, Cuiping Zhang, Yongcun Zhu, Job Tien Chiang Liu, Nicole Salazar, Shukun Zhang, Jiandi Zhang, Xiaosong Chen, Chaofu Wang
Institutions: Binzhou Medical University, Shanghai Jiao Tong University, Ruijin Hospital, Shandong University, Weihai Municipal Hospital, Henan Cancer Hospital, Third People's Hospital of Hefei, Xinjiang Medical University, Fifth Affiliated Hospital of Xinjiang Medical University, Xiangxi Tujia and Miao Autonomous Prefecture People's Hospital, North Carolina Central University
Language: English
Topic: HER2/EGFR in Cancer Research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
Funder: Binzhou Medical University
OpenAlex ID: W7155689458