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一名转移性PD-L1阳性乳腺癌且携带胚系BRCA1突变患者的获得性治疗耐药性

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

作者信息

Kumeta Toko, Yamaguchi Kei, Hayami Ryosuke, Arai Kazumori, Tsuneizumi Michiko, Matsunuma Ryoichi

机构信息

Department of Breast Surgery, Shizuoka General Hospital, Shizuoka, Japan.

Department of Pathology, Shizuoka General Hospital, Shizuoka, Japan.

出版信息

Case Rep Oncol. 2023 Jul 14;16(1):544-551. doi: 10.1159/000530131. eCollection 2023 Jan-Dec.

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 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 mutations. Here, we report a patient with metastatic PD-L1-positive TNBC who harbored a germline 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.

摘要

三阴性乳腺癌(TNBC)是一种侵袭性乳腺癌亚型,与其他亚型相比,其复发率和死亡率更高。由于缺乏治疗靶点,化疗一直是TNBC的主流治疗方法。最近的进展导致针对特定携带种系突变的程序性死亡配体1(PD-L1)阳性TNBC患者引入了新型药物。然而,一些对PD-L1或聚(ADP-核糖)聚合酶(PARP)抑制剂有反应的患者往往会产生耐药性。此外,对于PD-L1阳性TNBC和种系突变患者,治疗策略更为复杂。在此,我们报告一例携带种系突变的转移性PD-L1阳性TNBC患者。该患者先后接受了包括PD-L1抑制剂联合化疗和PARP抑制剂奥拉帕利在内的联合治疗方案,在几个月内对治疗产生了耐药性。有必要进行进一步研究,以阐明对PD-L1抗体和PARP抑制剂耐药的机制,从而改善治疗效果,同时防止TNBC患者出现治疗耐药性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed0f/10359695/95f891549baa/cro-2023-0016-0001-530131_F01.jpg

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