[Targeted therapies in neoadjuvant breast cancer: The role of CDK4/6 and PARP inhibitors]

Abstract

Over the past decade, targeted therapies have significantly improved the prognosis of metastatic breast cancer. CDK4/6 and PARP inhibitors are now gaining traction in the adjuvant setting, and their potential use in the neoadjuvant context is also being explored. This review presents an analysis of the current scientific evidence and associated clinical perspectives. CDK4/6 inhibitors act on cell cycle dysregulation, commonly observed in hormone receptor-positive breast cancers. In the adjuvant setting, abemaciclib and ribociclib have shown improvements in progression-free survival (PFS) in the monarchE and NATALEE trials, respectively, leading to their approval by the European Medicines Agency. In the neoadjuvant context, although these agents have demonstrated a reduction in proliferation markers such as Ki67, their impact on clinical practice remains limited to date. PARP inhibitors are based on the concept of synthetic lethality, specifically targeting cancers with germline BRCA1 or BRCA2 mutations. In the adjuvant setting, the OlympiA trial demonstrated a significant improvement in both PFS and overall survival (OS). In the neoadjuvant setting, these agents have also shown effects on pathological markers, though the clinical relevance of these findings has yet to be clearly established. Overall, these results underscore the growing role of targeted therapies in the adjuvant management of breast cancer. The identification and validation of predictive biomarkers will be crucial in optimizing their use, both in adjuvant and neoadjuvant settings.

Keywords: Adjuvant; Adjuvant setting; Breast cancer; CDK4/6 inhibitors; Cancer du sein; Inhibiteurs de CDK4/6; Inhibiteurs de PARP; Neoadjuvant; Neoadjuvant setting; PARP inhibitors.