20P Spatial analysis of residual tumor tissue provides new clues for post-neoadjuvant treatment approaches in triple-negative breast cancer

Triple-negative breast cancer (TNBC) is a very heterogeneous disease with high metastatic recurrence risk. We showed (PMID 34535679) that TNBCs relapsing rapidly (RR) after NACT (in ≤ 12 months) are highly proliferative, immune-cold, often large residual burden (RCB) and fatal outcome. No specific biomarkers or therapeutic targets known for this clinical category. In study we performed spatial molecular analysis of the RR RCB3 TNBCs, aim to help improving treatment TNBC patients poorest prognosis. analyzed tumor tissue samples treated by standard from 01/01/2009 31/12/2021. The cases were classified into RR, standardly-relapsing (SR, 1-5 years post-NACT) without recurrences (NR). amount tumor-infiltrating lymphocytes (TILs) was determined optical microscopy (H&E). Tissue protein expression spatially resolved GeoMx® Digital Spatial Profiler (NanoString Technology). Sixteen, 17 47 SR NR analyzed, respectively. GeoMx included 216 Region-of-Interest (ROIs) microenvironment (TME) 207 cells (TC), balanced (∼50/50) numbers peripheral (P) central (C) ROIs. Tumors ROIs TIL-rich (LR) TIL-poor (LP) using cut-off 10% TILs. higher Ki67, cleaved caspase 9, granzyme B (GZMB), FoxP3 fibronectin (FBNCT) in TME-P-LR but GADPH, TIM-3, PD-L1 IDO TME-P-LP Compared TNBC-SR, had GZMB CD34 TME-C-LR RRs, CD8 low, as well one CD45, CD3 TME-C-LP. category contained 8 10 cases, Although most TIL-poor, significantly CD3, CD8, GZMA, CD4, CD56, CD95, LAG3, HLA-DR, BIM BCL6 than cases. By revealed several potential (fibronectin, IDO, /angiogenesis) TNBCs. Interestingly, also some have immune-activated TME good crucial these discoveries.