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Olaparib + trastuzumab + pertuzumab is an investigational combination regimen being evaluated as a chemotherapy-free neoadjuvant therapy for elderly patients with HER2-positive breast cancer. The regimen combines three distinct targeted agents: **olaparib** (Lynparza), a small-molecule inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes (PARP1 and PARP2); **trastuzumab** (Herceptin), a monoclonal antibody targeting the extracellular domain IV of the HER2 receptor; and **pertuzumab** (Perjeta), a monoclonal antibody targeting the extracellular domain II of the HER2 receptor. By combining PARP inhibition with dual HER2 blockade, the regimen aims to exploit potential synthetic lethality in cancer cells while simultaneously suppressing the HER2 signaling pathway and preventing HER2 heterodimerization. This approach is specifically being studied in patients aged 60 and older to provide an effective treatment option with a more favorable toxicity profile compared to traditional chemotherapy-containing neoadjuvant regimens.
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