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使用聚(ADP-核糖)聚合酶(PARP)抑制剂和免疫检查点抑制剂治疗BRCA 1基因变异的乳腺癌。

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

作者信息

Hoppe Christina, Roubal Kiera, Pavuluri Sushma, Lupak Oleksandra

机构信息

Clinical Pharmacy Specialist - Hematology & Oncology, Medical University of South Carolina, Charleston, SC, USA.

Hematology & Oncology Fellow, Medical University of South Carolina, Charleston, SC, USA.

出版信息

J Oncol Pharm Pract. 2025 Jul;31(5):850-852. doi: 10.1177/10781552251320049. Epub 2025 Feb 17.

Abstract

IntroductionTriple 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 ReportA 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 OutcomeDue 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.DiscussionThere 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.

摘要

引言

三阴性乳腺癌(TNBC)传统上因其缺乏激素受体(HR)和人表皮生长因子受体2(HER2)而治疗具有挑战性,这些曾被视为乳腺癌治疗的唯一“靶点”。自2017年以来,奥拉帕利等靶向治疗方案已被批准用于治疗胚系乳腺癌基因(BRCA)突变的乳腺癌,以及用于TNBC的免疫检查点抑制剂。

病例报告

一名45岁女性在2018年被诊断为BRCA1突变的TNBC和卵巢癌,并部分完成了辅助治疗。2020年,她的CA - 125升高,开始使用奥拉帕利治疗。由于耐受性问题,她停止治疗并转为观察。2021年,影像学检查显示有脑转移,她开始使用卡培他滨治疗。2021年11月,她病情进展并将治疗转至我们这里。

治疗与结果

由于怀疑为双转移的TNBC和卵巢癌,且卵巢组织的综合阳性评分(CPS)为3,开始使用吉西他滨、卡铂和帕博利珠单抗治疗。六个周期后,影像学检查显示脑病变消退,继续使用帕博利珠单抗维持治疗。2023年3月,由于怀疑卵巢癌进展且乳腺癌消退,她改用卡铂、紫杉醇和贝伐单抗治疗。她持续使用该方案直至2023年12月,然后改用奥拉帕利和贝伐单抗治疗。

讨论

支持在聚(ADP - 核糖)聚合酶(PARP)抑制剂治疗后序贯使用免疫疗法的数据有限。此处呈现的病例报告证明了一名BRCA1突变的TNBC患者在奥拉帕利治疗后使用帕博利珠单抗获得成功治疗。

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