AUTHOR=Yang Dunya , Zhang Xiaoyu , Hu Xinyu , Lin Shaoqin , Yu Naying , Lin Xianglan , Chen Qunxiang , Chen Xi 

TITLE=Case Report: Fluzoparib combined Exemestane in gBRCA2-mutated HR+/HER2− advanced breast cancer

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1673418

DOI=10.3389/fphar.2025.1673418

ISSN=1663-9812

ABSTRACT=This case study details a 57-year-old woman with heavily pretreated, hormone receptor-positive (HR+), HER2-negative advanced breast cancer harboring a pathogenic germline BRCA2 mutation. Following progression on multiple prior therapies including endocrine therapy combined with a CDK4/6 inhibitor, chemotherapy, and an antibody-drug conjugate (resulting in liver metastases), blood-based next-generation sequencing (NGS) identified the gBRCA2 variant alongside persistent high ER expression. Guided by these molecular findings, treatment was initiated with the domestically developed, highly selective PARP inhibitor (PARPi) Fluzoparib (300 mg orally twice daily) combined with the aromatase inhibitor Exemestane (25 mg orally daily). The regimen was well-tolerated, with manageable grade 1–2 adverse events (anemia, nausea, rash). Follow-up imaging demonstrated complete resolution of the hepatic metastases. The patient achieved a remarkably prolonged progression-free survival (PFS) of 37 months on this combination therapy, representing the longest period of disease control in her metastatic course. Although eventual progression occurred (new axillary lymph node metastasis and suspected hepatic recurrence), this case demonstrates the exceptional efficacy and durable disease control achievable with Fluzoparib plus Exemestane in a pretreated patient with gBRCA2-mutated HR+/HER2-advanced breast cancer, highlighting a promising therapeutic approach for this molecularly defined population.