Acquired Treatment Resistance in a Patient with Metastatic PD-L1-Positive Breast Cancer and Germline BRCA1 Mutation

Abstract

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer associated with higher rates of relapse and mortality compared to other subtypes. Chemotherapy has been a mainstream treatment approach for TNBC due to the lack of therapeutic targets. Recent advances have led to the introduction of novel agents against specific patients with programmed death-ligand 1 (PD-L1)-positive TNBC who harbor germline <i>BRCA</i> mutations. However, some patients who respond to PD-L1 or poly (ADP-ribose) polymerase PARP inhibitors often develop resistance. Additionally, treatment strategies are more complicated for patients with PD-L1-positive TNBC and germline <i>BRCA</i> mutations. Here, we report a patient with metastatic PD-L1-positive TNBC who harbored a germline <i>BRCA1</i> mutation. The patient sequentially received combination treatment regimens, including PD-L1 inhibitors with chemotherapy and the PARP inhibitor olaparib, acquiring resistance to the treatments in a couple of months. Further investigations are warranted to elucidate the mechanisms underlying resistance to PD-L1 antibodies and PARP inhibitors to improve treatment outcomes while preventing emergence of treatment resistance in patients with TNBC.