A worldwide survey on pathological measurement of residual breast cancer after neoadjuvant therapy: different interpretations of the ypTNM classification
Kwakkenbos, Koen Van Bockstal, Mieke R Shaaban, Abeer M Brogi, Edi Cserni, Gabor Ellis, Ian O Foschini, Maria Pia Fox, Stephen B Bago-Horvath, Zsuzsanna Jaffer, Shabnam
Kwakkenbos, Koen
Van Bockstal, Mieke R
Shaaban, Abeer M
Brogi, Edi
Cserni, Gabor
Ellis, Ian O
Foschini, Maria Pia
Fox, Stephen B
Bago-Horvath, Zsuzsanna
Jaffer, Shabnam
Affiliation
Erasmus University Medical Centre; Cliniques universitaires Saint-Luc; Université catholique de Louvain; University of Birmingham; University Hospitals Birmingham NHS Foundation Trust; Memorial Sloan Kettering Cancer Center; University of Szeged; Bács-Kiskun County Teaching Hospital; Nottingham University Hospitals NHS Trust; Bellaria Hospital; University of Melbourne; Medical University of Vienna; Northwell Health Lenox Hill Hospital; King's College; Guy's and St Thomas' NHS Foundation Trust; Cambridge University Hospitals; St. Vincent's University hospital; University College Dublin; Hamad Medical Corporation; University of Nottingham; Flinders University; Flinders Medical Centre; Royal Square Medical Centre Singapore; The Chinese University of Hong Kong; University Hospital Zurich
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Publication date
2026-01-22
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Abstract
The extent of residual disease after neoadjuvant chemotherapy (NAC) in breast cancer (BC) patients holds prognostic value. However, current practices for reporting post-NAC BC specimens according to the ypTNM classification vary. This study aimed to map these practices and provide recommendations for standardization. A survey was developed and globally circulated to pathologists with a special interest in BC through personal networks and working group mailing lists. The survey included general questions about tumor diameter assessment, as well as graphical scenarios presenting different distributions of tumor cells. We did not provide definitions mentioned in reporting guidelines to capture unbiased current real-world practices. A total of 208 pathologists from 35 countries completed the survey. Almost all responding pathologists (97.1%) report the ypTNM in daily practice. Despite self-reported strict adherence to the 8th edition of the international ypTNM classification, we found substantial variation in practice concerning the application of this staging system, particularly in cases with an uneven distribution of scattered residual disease. Notably, 57.2% of respondents reported measuring the largest 'continuous cluster of tumor cells', but the interpretation of this definition varied widely. This international survey identifies the challenges and the practice heterogeneity in the current application of the ypTNM staging system, which hampers the value of ypTNM reporting in daily practice. To enhance reproducibility and to provide more reliable post-NAC risk stratification, we recommend adopting standardized reporting with clearer pattern-based definitions of the ypTNM guidelines, supplemented with the elements of the Residual Cancer Burden system.
Citation
Kwakkenbos K, Van Bockstal MR, Shaaban AM, Brogi E, Cserni G, Ellis IO, Foschini MP, Fox SB, Bago-Horvath Z, Jaffer S, Jager A, Pinder SE, Provenzano E, Quinn CM, Rakha EA, Raymond WA, Tan PH, Tse GM, Varga Z, Wen HY, van Deurzen CHM. A Worldwide Survey on Pathological Measurement of Residual Breast Cancer After Neoadjuvant Therapy: Different Interpretations of the ypTNM Classification. Mod Pathol. 2026 Jan 22:100963. doi: 10.1016/j.modpat.2026.100963. Epub ahead of print.
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Article