Report of a national external quality assessment program for HER2-low expression in breast cancer-options for increased accuracy with standardized methodology.

HER2-low breast cancer is an important new diagnostic tumor category with promising therapeutic options. The aim of this study was to evaluate the quality of HER2-low determination in a national prospective external quality assessment (EQA) and to identify pitfalls and options for improvement. Slides were distributed to 66 pathology institutions for diagnostic assessment according to pre-defined HER2-low categories. After local staining and evaluation, slides were collected for central re-evaluation for quality parameters. Endpoints included the percentage of correct HER2-assessments and subgroup analyses for selected technical parameters. Within this prospective proficiency test, a total of 659 individual HER2 evaluations were performed by 66 participating institutions with 86% correct results. Of the incorrect results, 82% (73 of 89) reported a HER2 category that was too high, and only 18% reported a category that was too low. A successful participation was achieved by 71% of 66 pathology institutions. In central re-evaluation, technical limitations were identified as the most important parameters for suboptimal results. In defined institutional subgroups with optimal technical parameters (antibodies, automation platforms and detection systems) a success rate of up to 86-91% was achieved. In this prospective EQA assessment, the concordance rate of pathology institutions is now much higher compared to previous retrospective studies. However, the quality assurance results are still lower compared to classical HER2 proficiency tests focusing on HER2 3 + tumors, and further optimization is necessary. The results will contribute to further improve the reliability of HER2 testing, which could also be applied to HER2-ultralow in the future.