ARTEMIS (AC neoadjuvant chemo) links “immune hot/cold” contexture to pCR in early TNBC

ARTEMIS (NCT02276443) tested whether adding a gene-expression molecular classifier could better select early-stage triple-negative breast cancer (TNBC) patients for neoadjuvant doxorubicin/cyclophosphamide (AC) alone, but the classifier did not significantly improve pathologic complete response (pCR) (33%→41%, p=0.43). The strongest correlates of AC response were immune features, enabling three immune subtypes—“immune hot sensitive,” “immune hot resistant,” and “immune cold”—with pCR of 50% in immune hot tumors vs 8% in immune cold tumors; immune-cold disease also showed mesenchymal biology and FGF/TGF-β signaling signatures that may be actionable. Clinically, this doesn’t yet beat today’s neoadjuvant chemo-IO benchmark (e.g., pembrolizumab + chemo pCR ~65% vs ~51% with chemo alone in KEYNOTE-522), but it sharpens who might safely de-escalate to chemo-only vs who needs alternative/add-on strategies.