Effectiveness and safety of PARP inhibitors in breast cancer

Background Breast cancer is a leading cause of cancer-related mortality in women worldwide. Poly(ADP-ribose) polymerase inhibitors (PARPi) have shown efficacy in improving progression-free survival (PFS), particularly in patients with breast cancer susceptibility genes 1 and 2 (BRCA1/2) mutations and homologous recombination deficiency (HRD). Methods This umbrella review of systematic reviews and meta-analyses assessed the effectiveness and safety of PARP inhibitors (PARPi) across various breast cancer subtypes. Results PARPi significantly improved PFS and overall response rate (ORR), especially in BRCA-mutated and triple-negative breast cancer (TNBC) populations. However, overall survival (OS) benefits were modest and often not statistically significant. PARPi treatment was associated with increased risks of anemia, neutropenia, and gastrointestinal toxicities, although the rates of overall Grade ≥ 3 adverse events were comparable to those of chemotherapy. Conclusions This review highlights the clinical value of PARP inhibitors (PARPi), particularly in genetically defined subgroups, and underscores the need for biomarker-driven treatment strategies and further exploration of combination regimens.