Emergence of PALB2 Reversion Mutations as a Mechanism of Resistance to Niraparib in Breast Cancer: A Case Report

This case study describes the clinical course of a 39‐year‐old woman with metastatic breast cancer harboring a germline PALB2 mutation who was treated with a PARP inhibitor. She initially demonstrated a clinical benefit with reduced tumor markers and favorable imaging findings. However, disease progression occurred after eight months. Liquid biopsy‐based genomic profiling identified three PALB2 reversion mutations that restored homologous recombination, leading to treatment resistance. The case illustrates both the therapeutic potential of PARP inhibitors in PALB2‐mutated cancers and the emergence of resistance. It emphasizes the importance of liquid biopsy‐based genomic profiling for understanding tumor evolution and guiding treatment strategies.