PARP Inhibition as an Effective Therapeutic Strategy in Disseminated TNBC with Extensive CNS Metastases: A Case Report

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by early metastatic spread, limited treatment options and poor prognosis. We describe the case of a 55-year-old woman who presented with disseminated TNBC (lymph nodes, peritoneal and visceral metastasis) and extensive supra- and infratentorial brain metastases. First-line treatment with paclitaxel plus pembrolizumab according to the KEYNOTE-355 trial resulted in an initial systemic and intracranial response; however, progression occurred after four cycles of treatment. Molecular profiling using circulating tumor (ct)DNA-based next-generation sequencing identified a pathogenic somatic *BRCA2* splice-site mutation, enabling the initiation of targeted therapy with the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib after first-line chemoimmunotherapy. Under olaparib treatment, the patient achieved partial remission with regression of both systemic and central nervous system disease and sustained clinical benefit with good tolerability. This case highlights the importance of comprehensive molecular testing and flexible treatment sequencing in patients with advanced TNBC. PARP inhibition may provide meaningful systemic and intracranial disease control in *BRCA2*-mutated TNBC, even after progression on first-line chemoimmunotherapy. PEER REVIEWED ARTICLE **Peer reviewers** Prof. Dr Rupert Bartsch, Division of Oncology, Medical University of Vienna, Vienna, Austria PD Dr Mattea Reinisch, Interdisciplinary Breast Unit, University Hospital Mannheim, Mannheim, Germany Received on December 17, 2025; accepted after peer review on February 06, 2026; published online on February 09, 2026.