Abstract
BRCA1 mutation is closely linked to triple-negative breast cancer (TNBC), a subtype characterized by early onset, aggressive clinical course, and marked genomic instability. Although poly ADP ribose polymerase (PARP) inhibitors have expanded treatment options, resistance driven by cancer stem cells (CSCs) and incomplete interception of premalignant progression remain pressing challenges. In a recent study, Liu et al. developed a human induced pluripotent stem cell (iPSC)-based breast cancer model that follows BRCA1‑driven tumorigenesis from mammary differentiation to invasive disease and identify S100P as a BRCA1‑repressed effector associated with cancer stemness. These findings provide a human genetic context to probe early oncogenesis and nominate the S100P–RAGE axis as a precautionary—but promising—target for risk interception.