Resistance to PARP Inhibitors After First-Line Platinum-Based Chemotherapy in a Patient with Advanced Ovarian Cancer with a Pathogenic Somatic BRCA1 Mutation

Abstract

PARP inhibitors (PARPi) are the maintenance therapy after first line platinum-based chemotherapy for patients with advanced epithelial ovarian cancer (EOC) with germline and pathogenic somatic BRCA1/2 mutations. However, as with chemotherapy, patients can develop resistance to PARPi. The selective pressure generated by heterogeneous somatic BRCA mutations may give rise to chemotherapy or PARPi resistant tumors. Here, we present the case of a patient harboring a pathogenic p.Glu143* (c.427G>T) somatic BRCA1 mutation conferring resistance to olaparib following cytoreductive surgery and platinum-based chemotherapy. We ordered a plasma ctDNA analysis (tissue biopsy of recurrent lesions was contraindicated due to their anatomical location) to figure out the possible resistance mechanism. Analysis of ctDNA did not detect the pathogenic somatic BRCA1 p.Glu143* (c.427G>T) mutation seen before. The tumor cells harboring the pathogenic BRCA1 mutation were probably eliminated by the platinum-based chemotherapy, leaving only those without BRCA mutations to proliferate.

Keywords:

• PARPi resistance
• BRCA1 mutation
• ovarian carcinoma
• circulating tumor DNA
• sequencing

Patient Consent Statement

Written informed consent was obtained from the patient for the publication of this case report. The study was approved by the Ethics Committee of West China Second University Hospital of Sichuan University (approval number: 2020076).

Acknowledgments

The study was supported grants from the Key Project of Science and Technology Department of Sichuan province (CN) (19ZDYF), New Seed Fund of West China Second University Hospital, Sichuan University (kz022) and Horizontal Topic of Sichuan University (22H0226, 22H0851).

Disclosure

All authors declare no conflicts of interest in this work.