FOXA1/EZH2 Dual IHC as a Point-of-Care Breast Cancer Decision Tool: Two Stains, One Number, Six Subtypes — A Universal Treatment Stratification Instrument Derived from Waddington Attractor Geometry
Abstract
Breast cancer treatment stratification currently relies on PAM50/Prosigna (NanoString nCounter, $3,000–$4,000 per patient) for molecular subtyping, limiting precision oncology to major centres in wealthy countries. We report the derivation and multi-dataset validation of the FOXA1/EZH2 ratio as a two-stain IHC instrument for simultaneous subtype classification and treatment logic assignment across all six major breast cancer subtypes (Luminal A, Luminal B, HER2-enriched, TNBC, Claudin-low, and ILC). The ratio was derived from Waddington attractor geometry applied to 19,542 single cancer cells (GSE176078), where it correctly orders subtypes in the predicted sequence LumA > LumB > HER2 > TNBC > Claudin-low (values: LumA 9.38, LumB 8.10, HER2 3.34, TNBC 0.52, CL 0.10). This ordering was confirmed in TCGA-BRCA (n=837 PAM50-labelled patients, KW p=2.87×10^-103), with survival stratification confirmed in TCGA-BRCA (KM p=0.0031, n=1,218) and METABRIC (KM p8 (luminal, ET engages; LumA vs LumB distinguished by CDK4/6i vs HDACi); ratio ~3 (HER2 amplicon, anti-HER2 first); ratio ~0.5 (epigenetic lock, tazemetostat + fulvestrant sequence); ratio
Fields of Study & Subjects
Breast Cancer Treatment Studies
Breast Lesions and Carcinomas
HER2/EGFR in Cancer Research
Publication details
- Journal / source
- Zenodo (CERN European Organization for Nuclear Research)
- Publication date
- 6 March 2026
- Language
- EN
- Document type
- Preprint