Treatment of BRCA 1 mutated breast cancer with a PARP inhibitor and an Immune Checkpoint Inhibitor

Abstract

Introduction

Triple negative breast cancer (TNBC) has traditionally been challenging to treat due to its lack of hormone receptors (HR) and human epidermal growth factor receptor 2 (HER2), which were perceived as the only “targets” for treatment of breast cancer. Since 2017, targeted treatment options, such as olaparib, have been approved for the treatment of germline BReast CAncer gene (BRCA) mutated breast cancer, and immune checkpoint inhibitors for TNBC.

Case Report

A 45-year-old female was diagnosed with BRCA1 mutated TNBC and ovarian cancer in 2018, and adjuvant treatment was partially completed. In 2020, her CA-125 rose and olaparib was initiated. Due to tolerability, she stopped treatment and transitioned to surveillance. In 2021, imaging showed brain metastases, and she started capecitabine. In November 2021 she progressed and transferred care to us.

Management and Outcome

Due to suspected dual metastatic TNBC and ovarian cancers, and ovarian tissue demonstrating a combined positive score (CPS) of 3, gemcitabine, carboplatin and pembrolizumab were initiated. After six cycles, imaging demonstrated resolution of brain lesions, and pembrolizumab maintenance was continued. In March 2023, she switched to carboplatin, paclitaxel and bevacizumab, due to suspected progression of her ovarian cancer and resolution of breast cancer. She continued until December 2023 and switched to olaparib and bevacizumab.

Discussion

There is limited data to support sequential use of immunotherapy following treatment with a poly (ADP-ribose) polymerase (PARP) inhibitor. The case report presented here demonstrates successful treatment of a patient with BRCA1 mutated TNBC treated with pembrolizumab after olaparib.

Keywords

Triple negative breast cancer immune checkpoint inhibitor BRCA mutation PARP inhibitor sequential therapy

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