a Overview of the 3-step approach for characterizing spatial molecular patterns shared across TNBC samples, leading to the identification of 14 megaclusters and 9 spatial archetypes. b Projection of intra-patient (top) and inter-patient (bottom) clusters in a representative BL subtype TNBC sample (ST_TNBC_ID 30). c Heterogeneity of intra-patient clusters based on TNBC molecular classification (N = 94). The TNBC molecular subtype was calculated using global pseudobulk (Subtype PB), with spatial immunophenotypes (TIME) also shown. d Morphological, molecular, and cellular characterization of the 14 megaclusters shared across TNBC patients (N = 94). The molecular subtypes of the 418 individual clusters are shown (% TNBC subtype). A heatmap of selected molecular features (single gene expression, gene signatures, and xCell cell type enrichment) specific to each megacluster is provided, with detailed analyses available in Supplementary Figs. 11b, c, 12, and 13. e, f Association of the 14 megaclusters with iBCFS in the ST TNBC cohort (N = 94) (e) and the combined METABRIC and SCAN-B cohorts (N = 1007) (f), using deconvolution of ST spots and RNA bulk expression, respectively. Analyses were adjusted for age, tumor size, and nodal status. Two-sided P values were derived from likelihood ratio tests on nested models, with significant FDRs (<0.05) shown in blue. Circles represent HR, and error bars indicate the 95% CI. Source data are provided as a Source Data file. BL basal-like, C1-C7 individual clusters 1–7, CAF cancer-associated fibroblast, CI confidence interval, DC dendritic cells, Dec deconvolution, EMT epithelial-mesenchymal transition, FDR false-discovery rate, FI full inflamed, GGI genomic grade index, HR hazard ratio, iBCFS invasive breast cancer-free survival, ID immune desert, IM immunomodulatory, KM K-means, LAR luminal androgen receptor, M mesenchymal, MC megacluster, MR margin restricted, MSL mesenchymal stem-like, PB pseudobulk, SA spatial archetype, SR stroma restricted, TAM tumor associated macrophages, Th2 type 2 helper, TIME Tumor Immune Micro-Environment, TLS tertiary lymphoid structure, TNBC triple-negative breast cancer, Trm tissue-resident memory T cell, VCpredTN veliparib carboplatin prediction triple negative.