The Changes in BRCA Mutation Status and Their Impact on Recurrence in Ovarian Cancer Patients After Oral PARPi Treatment

Background The present study was designed to investigate the genetic mutations in patients with recurrent ovarian cancer (OC), with a particular focus on comparing the genetic profiles prior to and following relapse in individuals who had previously been treated with Olaparib. Methods This retrospective study enrolled nine patients with OC between November 2017 and October 2023. Eligible patients were required to have histologically confirmed OC, prior BRCA1/2 genetic testing, and a history of receiving Olaparib as maintenance therapy. Patients were subsequently divided into two groups based on the timing of their BRCA1/2 testing. Comprehensive analysis of BRCA1/2 mutations was performed using a combination of sequencing and multiplex ligation-dependent probe amplification (MLPA). Results Among 9 OC patients analyzed, platinum-sensitive recurrence was observed. Frameshift and splice mutations in BRCA1/2 were identified as significant factors associated with disease progression and poor prognosis. Moreover, TP53 alterations were frequently detected in conjunction with FGFR3 or PIK3CA mutations. While PARP inhibitor (PARPi) therapy effectively extended progression-free survival, resistance eventually developed through secondary mutations and activation of bypass repair pathways. Conclusions In OC patiens, BRCA1/2 mutations, encompassing frameshift and splice variants, and copy number losses are linked to higher recurrence rates and reduced progression-free survival (PFS). Extended Olaparib treatment is associated with improved PFS, whereas shorter treatment durations may contribute to the emergence of resistance.