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三阴性乳腺癌:文献系统综述中的分子和临床特征,重点是创新药物治疗。

Triple-Negative Breast Cancers: Systematic Review of the Literature on Molecular and Clinical Features with a Focus on Treatment with Innovative Drugs.

机构信息

Division of Medical Oncology, Department of Precision Medicine, Università degli Studi della Campania Luigi Vanvitelli, II Policlinico via S. Pansini, 5, 80131, Naples, Italy.

出版信息

Curr Oncol Rep. 2018 Aug 20;20(10):76. doi: 10.1007/s11912-018-0726-6.

DOI:10.1007/s11912-018-0726-6
PMID:30128845
Abstract

PURPOSE OF REVIEW

Triple-negative breast cancer (TNBC) accounts for 15-20% of diagnosed breast tumours, with higher incidence in young and African-American women, and it is frequently associated with BRCA germline mutations. Chemotherapy is the only well-established therapeutic option in both early- and advanced-stages of the disease. TNBC tumours relapse earlier after standard anthracycline- and/or taxane-based chemotherapy treatments, generally within 1-3 years after the diagnosis, and often develop visceral metastases, representing the subtype with a worse prognosis among all breast cancers. In the present review, we will provide an updated overview of the available results of recent clinical trials for this disease and we will describe the implications of the known molecular pathways representing novel targets for development of future therapies for TNBC patients.

RECENT FINDINGS

Over the past decade, the advent of gene expression micro-array technology has led to the identification of different actionable targets including various genomic alterations, androgen receptor, PARP, PI3K, VEGF and other proteins of the angiogenic pathway. Thus, novel targeted drugs have been tested in clinical trials reporting promising results in specific TNBC molecular subgroups. Although cytotoxic chemotherapy remains the mainstay of treatment for TNBC patients, the identification of novel 'drugable' targets and pathways for developing personalized treatments represents a promising investigational approach in the management of the TNBC subtype.

摘要

目的综述

三阴性乳腺癌(TNBC)占诊断出的乳腺癌的 15-20%,在年轻和非裔美国女性中发病率更高,并且常与 BRCA 种系突变有关。在疾病的早期和晚期阶段,化疗是唯一经过充分验证的治疗选择。与基于蒽环类药物和/或紫杉烷的标准化疗治疗相比,TNBC 肿瘤在标准治疗后更早复发,通常在诊断后 1-3 年内,并且经常发生内脏转移,是所有乳腺癌中预后最差的亚型。在本综述中,我们将提供该疾病最近临床试验的最新结果概述,并描述已知分子途径的意义,这些途径代表了为 TNBC 患者开发未来治疗方法的新靶点。

最新发现

在过去十年中,基因表达微阵列技术的出现导致了不同可操作靶点的鉴定,包括各种基因组改变、雄激素受体、PARP、PI3K、VEGF 和血管生成途径的其他蛋白质。因此,新型靶向药物已在临床试验中进行了测试,这些试验报告了特定 TNBC 分子亚组中的有希望的结果。尽管细胞毒性化疗仍然是 TNBC 患者治疗的主要方法,但鉴定新的“可治疗”靶点和途径以开发个性化治疗方法代表了管理 TNBC 亚型的一种很有前途的研究方法。

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Addition of the PARP inhibitor veliparib plus carboplatin or carboplatin alone to standard neoadjuvant chemotherapy in triple-negative breast cancer (BrighTNess): a randomised, phase 3 trial.在三阴性乳腺癌(BrighTNess)中,将 PARP 抑制剂 veliparib 联合卡铂或卡铂单药添加到标准新辅助化疗中:一项随机、3 期试验。
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Enzalutamide for the Treatment of Androgen Receptor-Expressing Triple-Negative Breast Cancer.恩杂鲁胺治疗雄激素受体表达的三阴性乳腺癌。
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ANKRD1 Promotes Breast Cancer Metastasis by Activating NF-B-MAGE-A6 Pathway.
锚蛋白重复结构域1通过激活核因子-κB-黑色素瘤抗原基因A6通路促进乳腺癌转移。
Cancers (Basel). 2024 Sep 27;16(19):3306. doi: 10.3390/cancers16193306.
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Real world study of sacituzumab govitecan in metastatic triple-negative breast cancer in the United Kingdom.英国转移性三阴性乳腺癌中 sacituzumab govitecan 的真实世界研究。
Br J Cancer. 2024 Jun;130(12):1916-1920. doi: 10.1038/s41416-024-02685-9. Epub 2024 Apr 24.
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Unveiling Epigenetic Vulnerabilities in Triple-Negative Breast Cancer through 3D Organoid Drug Screening.通过3D类器官药物筛选揭示三阴性乳腺癌中的表观遗传脆弱性
Pharmaceuticals (Basel). 2024 Feb 8;17(2):225. doi: 10.3390/ph17020225.
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Insights into the Emerging Therapeutic Targets of Triple-negative Breast Cancer.三阴乳腺癌新兴治疗靶点的见解
Curr Cancer Drug Targets. 2025;25(1):3-25. doi: 10.2174/0115680096280750240123054936.
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New triazole-based coordination complexes as antitumor agents against triple negative breast cancer MDA-MB-468 cell line.新型基于三唑的配位络合物作为抗三阴性乳腺癌MDA-MB-468细胞系的抗肿瘤剂。
RSC Adv. 2023 Dec 12;13(51):36158-36167. doi: 10.1039/d3ra07714d. eCollection 2023 Dec 8.
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Facts and prospects of peptide in targeted therapy and immune regulation against triple-negative breast cancer.三阴性乳腺癌靶向治疗和免疫调节中肽的现状与展望。
Front Immunol. 2023 Aug 25;14:1255820. doi: 10.3389/fimmu.2023.1255820. eCollection 2023.
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Nigericin Boosts Anti-Tumor Immune Response via Inducing Pyroptosis in Triple-Negative Breast Cancer.尼日利亚菌素通过诱导三阴性乳腺癌细胞焦亡增强抗肿瘤免疫反应
Cancers (Basel). 2023 Jun 16;15(12):3221. doi: 10.3390/cancers15123221.
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Ipatasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer (LOTUS): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial.
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Lancet Oncol. 2017 Oct;18(10):1360-1372. doi: 10.1016/S1470-2045(17)30450-3. Epub 2017 Aug 8.
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J Clin Oncol. 2017 Jul 1;35(19):2141-2148. doi: 10.1200/JCO.2016.70.8297. Epub 2017 Mar 14.
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Prognostic value of androgen receptor in triple negative breast cancer: A meta-analysis.雄激素受体在三阴性乳腺癌中的预后价值:一项荟萃分析。
Oncotarget. 2016 Jul 19;7(29):46482-46491. doi: 10.18632/oncotarget.10208.
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A phase II trial of abiraterone acetate plus prednisone in patients with triple-negative androgen receptor positive locally advanced or metastatic breast cancer (UCBG 12-1).阿比特龙联合泼尼松治疗三阴性雄激素受体阳性局部晚期或转移性乳腺癌患者的 II 期临床试验(UCBG 12-1)。
Ann Oncol. 2016 May;27(5):812-8. doi: 10.1093/annonc/mdw067. Epub 2016 Feb 18.
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Homologous Recombination Deficiency (HRD) Score Predicts Response to Platinum-Containing Neoadjuvant Chemotherapy in Patients with Triple-Negative Breast Cancer.同源重组缺陷(HRD)评分可预测三阴性乳腺癌患者对含铂新辅助化疗的反应。
Clin Cancer Res. 2016 Aug 1;22(15):3764-73. doi: 10.1158/1078-0432.CCR-15-2477. Epub 2016 Mar 8.
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