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Updated: Aug 4, 2025

Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells
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PARP Inhibitors for the Treatment of BRCA1/2-Mutated Metastatic Breast Cancer: A Systematic Review and Meta-analysis

Ranju Kunwor1, Daniel P Silver1,2, Maysa Abu-Khalaf1

  • 1Sidney Kimmel Cancer Center at Jefferson Health, Philadelphia, PA, USA.

Hematology/Oncology and Stem Cell Therapy
|April 6, 2023
PubMed
Abstract

Insights

Poly (ADP-ribose) polymerase inhibitors (PARPis) significantly improve progression-free survival (PFS) in metastatic breast cancer (MBC) patients with germline BRCA1/2 mutations (gBRCA+). However, overall survival (OS) benefits were not statistically significant compared to standard chemotherapy.

Area of Science:

  • Oncology
  • Genetics
  • Pharmacology

Background:

  • Metastatic breast cancer (MBC) with germline BRCA1/2 mutations (gBRCA+) has limited treatment options.
  • PARP inhibitors (PARPis) olaparib and talazoparib are approved for gBRCA+ MBC based on progression-free survival (PFS) benefits.
  • This meta-analysis evaluates the PFS and overall survival (OS) benefits of PARPis in gBRCA+ MBC.

Approach:

  • Systematic search of randomized controlled trials (RCTs) in major databases up to March 2021.
  • Included phase II and III RCTs comparing PARPis (alone or with chemotherapy) to standard chemotherapy.
  • Pooled analysis of hazard ratios (HR) for PFS and OS using RevMan v5.4.

Key Points:

  • Five RCTs with 1563 gBRCA+ MBC patients were analyzed.
  • PARPis significantly improved PFS compared to standard chemotherapy (HR, 0.64; P < 0.00001).
  • No statistically significant difference in OS (HR, 0.89; P = 0.09) or adverse events (OR, 1.18; P = 0.33) was observed.

Conclusions:

  • PARPis offer a significant PFS benefit over standard chemotherapy for gBRCA+ MBC.
  • The OS benefit of PARPis is comparable to standard chemotherapy.
  • Ongoing trials are investigating PARPis in earlier stages of gBRCA+ breast cancer.

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