PARP Inhibitors: A Major Therapeutic Option in Endocrine-Receptor Positive Breast Cancers

Area of Science:

• Oncology
• Genetics
• Pharmacology

Background:

• PARP inhibitors (PARPi) demonstrate a favorable efficacy/toxicity ratio versus chemotherapy in HER2-negative metastatic breast cancer (mBC) with BRCA mutations.
• PARPi are established in triple-negative mBC, but their role in ER+/HER2- mBC requires further definition.
• BRCA pathogenic variant (PV) carrier frequencies in ER+/HER2- breast cancer are underestimated.

Purpose of the Study:

• To identify ER+/HER2- mBC patients most likely to benefit from PARPi therapy.
• To review the current evidence on PARPi efficacy in specific breast cancer subtypes.
• To highlight the importance of early genotyping for treatment selection.

Main Methods:

• Narrative review of existing clinical trial data and literature.
• Analysis of patient populations in OlympiAD, EMBRACA, and OLYMPIA trials.
• Discussion of biomarker-driven treatment strategies.

Main Results:

• ER+/HER2- BRCA-mutated mBC patients may experience earlier progression on CDK4/6 inhibitors.
• PARPi demonstrate efficacy, particularly before chemotherapy exposure.
• PARPi are effective in high-risk early breast cancer patients with BRCA PVs (OLYMPIA trial).
• PARPi may benefit patients with homologous recombination deficiency (HRD) diseases, up to 20% of ER+/HER2- breast cancers.

Conclusions:

• PARPi represent a valuable therapeutic option for selected ER+/HER2- mBC patients.
• Early identification of BRCA PVs and HRD is crucial for optimizing PARPi use.
• Future implementation of early genotyping strategies is essential for personalized breast cancer treatment.