Lehmann classification (Vanderbilt Classification) of TNBC subtypes.
| Subtype | Key molecular features/Characteristics | Potential targeted therapy |
|---|---|---|
| Basal-like 1[6, 11] | High expression of DDR genes (e.g., ATR/BRCA pathway) and proliferation genes; high genomic instability. Frequently associated with BRCA1/2 mutations. | PARP inhibitors, platinum-based chemotherapy (cisplatin, carboplatin), and DNA repair pathway inhibitors (e.g., ATM, DNAPK inhibitors). |
| Basal-like 2[6, 11, 26] | Activation of growth factor signaling pathways (e.g., EGFR, MET, IGF-1R, Wnt/β-catenin); enrichment of glycolysis and gluconeogenesis pathways; expression of myoepithelial markers. | Growth factor inhibitors (e.g., lapatinib, gefitinib, cetuximab), MAPK pathway inhibitors, mTOR inhibitors, and CDK4/6 inhibitors. |
| Mesenchymal[6, 11] | High expression of genes involved in EMT, motility, adhesion, and stem cell pathways (e.g., Wnt/β-catenin, TGF-β, VEGF, mTOR, PI3K/AKT). Exhibits sarcoma-like tissue characteristics and is associated with drug resistance. | Src inhibitors (Dasatinib), PI3K/mTOR inhibitors, inhibitors targeting EMT pathways, Wnt pathway inhibitors, and retinoic acid derivatives. |
| Luminal androgen receptor [6, 10, 11, 18] | High expression of AR and AR-activated signaling (e.g., steroid biosynthesis, androgen/estrogen metabolism); frequently exhibits PIK3CA mutations. | Anti-AR therapies (e.g., bicalutamide, enzalutamide, abiraterone), PI3K/AKT/mTOR pathway inhibitors, and potentially CDK4/6 inhibitors (ribociclib, palbociclib). |
| Immunomodulatory [6, 11, 14, 18] | High levels of TILs; enriched for immune signaling pathways (T-cell receptor, cytokine signaling); high expression of immune checkpoints (PD-1/PD-L1). | ICIs such as anti-PD-1 (pembrolizumab) or anti-PD-L1 (atezolizumab) agents, and potentially anti-CTLA-4 inhibitors. |
AKT: protein kinase B; AR: androgen receptor; ATM: ataxia-telangiectasia mutated; ATR: ataxia telangiectasia and Rad3-related; CDK: cyclin-dependent kinase; CTLA-4: cytotoxic T-lymphocyte-associated protein 4; DDR: DNA damage response; EGFR: epidermal growth factor receptor; EMT: epithelial-to-mesenchymal transition; ICIs: immune checkpoint inhibitors; IGF-1R: insulin-like growth factor 1 receptor; MAPK: mitogen-activated protein kinase; MET: mesenchymal-epithelial transition; mTOR: mammalian target of rapamycin; PI3K: phosphoinositide-3 kinase; TGF-β: transforming growth factor beta; TILs: tumor-infiltrating lymphocytes; VEGF: vascular endothelial growth factor.