Published on February 10, 2025, in Cancer Cell, this international effort led by Carsten Denkert and colleagues investigates the dynamics of therapy-induced molecular heterogeneity in high-risk HR+/HER2− breast cancer, using longitudinal data from the Penelope-B trial.
The study uncovers that traditional intrinsic subtypes (like LumA and LumB) shift during the treatment journey—specifically, a transition from LumB to LumA after neoadjuvant chemotherapy, then a reverse shift back to LumB in metastatic disease. Going further, the team identified five adaptive clusters (AC1–AC5) based on transcriptomic changes. These clusters offer prognostic value beyond standard subtyping, with AC-5 showing very poor prognosis and enriched in basal-like features.
This analysis highlights how adaptive molecular subtyping could refine risk assessment and potentially guide post-neoadjuvant treatment in HR+/HER2− patients.
Thanks to all the contributors including Sibylle Loibl, Miguel Martin, Hope S Rugo, Nicholas Turner, Angela DeMichele, and others.
Read More: https://lnkd.in/dCkB7-YF
