PARP Inhibitor in BRCA Breast Cancer — RACP Adult Medicine MCQ

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ModerateMedical OncologyPARP Inhibitor in BRCA Breast CancerRACP Adult Medicine

A 45-year-old woman with known BRCA1 mutation and metastatic triple-negative breast cancer has progressed on two prior lines of chemotherapy. Her tumour is HRD (homologous recombination deficient). What targeted agent may benefit her?

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Correct answer: E — CDK4/6 inhibitor (palbociclib)

PARP inhibitors (olaparib, talazoparib) exploit synthetic lethality in BRCA-mutated/HRD tumours – tumour cells with defective homologous recombination (from BRCA1/2 mutation) cannot repair DNA double-strand breaks when PARP is inhibited, leading to cell death. The OlympiAD trial showed olaparib improved PFS in germline BRCA-mutated HER2-negative metastatic breast cancer. Olaparib is PBS-listed for this indication. Adverse effects include fatigue, nausea, anaemia, and small risk of MDS/AML with prolonged use.

Reference: Cancer Council Australia – 2024 – Breast Cancer Guidelines; PBS – 2025 – Olaparib Listing