Validation of pathology-based triage for the 21-gene recurrence score: A meta-analysis and qualitative synthesis of the Magee equations.
Issued Date
2026-05-27
Resource Type
ISSN
0732183X
eISSN
15277755
Scopus ID
2-s2.0-105041986990
Journal Title
Journal of Clinical Oncology
Volume
44
Issue
16
Start Page
1591
End Page
1591
Rights Holder(s)
SCOPUS
Bibliographic Citation
Journal of Clinical Oncology Vol.44 No.16 (2026) , 1591-1591
Suggested Citation
Susiriwatananont T., Eiamprapaporn P., Sakornsakolpat P., Thanestada J., Ma Y., Liu Y., Thompson E.A., Chumsri S. Validation of pathology-based triage for the 21-gene recurrence score: A meta-analysis and qualitative synthesis of the Magee equations.. Journal of Clinical Oncology Vol.44 No.16 (2026) , 1591-1591. 1591. doi:10.1200/JCO.2026.44.16_suppl.1591 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/117497
Title
Validation of pathology-based triage for the 21-gene recurrence score: A meta-analysis and qualitative synthesis of the Magee equations.
Author's Affiliation
Corresponding Author(s)
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Abstract
Background: The 21-gene OncotypeDX (ODX) recurrence score (RS) is the standard for chemotherapy decision-making in HR+/HER2- early breast cancer (EBC), but cost limits accessibility in resource-constrained settings. The Magee equations (MEs) use routine pathology features (Nottingham grade and IHC; ER/PR/HER2/Ki-67) to estimate RS. We performed a meta-analysis to validate MEs performance as a triage tool for ODX testing and a qualitative synthesis to identify sources of discordance, highlighting the transition toward objective digital pathology AI models. Methods: A systematic review identified validation studies comparing MEs with RS in HR+ EBC. Studies with sufficient data to construct a 2X2 contingency table were included; neoadjuvant trials were excluded. Primary outcomes were Negative Predictive Value (NPV) for identifying low-risk cases (RS <26 for the current TAILORx cutoff and RS<31 for the historical cutoff) and ODX test sparing rate (TSR). Data were pooled using random-effects models. Qualitative themes regarding interpretation variability were extracted from study results and discussion sections. Results: Thirteen studies met the inclusion criteria, representing 5396 patients in global cohorts from the USA, Mexico, Colombia, Jordan, France, Belgium, and Canada. For RS >26, Magee <18 achieved pooled NPV of 0.96 (95% CI: 0.94-0.97) and TSR 61% (95% CI:51%-69%). For RS >31, NPV increased to 0.99 (95% CI: 0.97-1.00) and TSR 52% (95% CI: 44%-59%). Pooled diagnostic performance for Magee <18 predicting RS <26 demonstrated 83% sensitivity and 71% specificity (AUC 0.81, LR+:2.53, LR-:0.28). Qualitative analysis of discordance identified: (1) Inter-observer variability: Nottingham mitotic counts and Ki-67 scoring were the primary drivers of score fluctuations. (2) IHC quantification: Variations in H-score calculation and Allred-to-H-score conversion introduced heterogeneity (3) Pre-analytical and biological factors: Inflammation and stromal proliferation occasionally inflated genomic RS; selection of non-representative blocks and intratumor heterogeneity further contributed to discordance (4) Technological solutions: Digital pathology and AI models emerge as solutions to standardize these variables. Conclusions: Magee-based triage provides a safe and cost-effective strategy for HR+ EBC risk stratification, with NPV up to 99% for excluding high-risk disease and sparing up to 61% of ODX testing. These results confirm a robust histopathological signal. Transitioning to objective digital pathomics provides a pathway to reduce manual subjectivity and democratize precision oncology globally.