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三阴性乳腺癌的新辅助治疗:铂类化疗、PARP 和免疫检查点抑制剂活性和疗效的潜在预测生物标志物。

Neoadjuvant therapy for triple-negative breast cancer: potential predictive biomarkers of activity and efficacy of platinum chemotherapy, PARP- and immune-checkpoint-inhibitors.

机构信息

Oncologia Medica, Fondazione Policlinico Universitario Agostino Gemelli IRCCS , Roma, Italy.

Università Cattolica Del Sacro Cuore , Roma, Italy.

出版信息

Expert Opin Pharmacother. 2020 Apr;21(6):687-699. doi: 10.1080/14656566.2020.1724957. Epub 2020 Feb 13.

Abstract

INTRODUCTION

Despite recent advances in the molecular characterization of triple-negative breast cancer (TNBC), the standard treatment for early-stage TNBC is represented by the historically used anthracycline and taxane-based chemotherapy. In this modern era of precision medicine, several new therapeutic strategies and novel agents have been investigated in the neoadjuvant setting of TNBC, in order to individualize treatment.

AREAS COVERED

This review provides a comprehensive overview of the currently available evidence regarding the activity and efficacy of platinum agents, PARP- and immune-checkpoint-inhibitors for the neoadjuvant treatment of TNBC, highlighting the available data on potential predictive biomarkers of response or resistance to such treatments.

EXPERT OPINION

The genomic and immune landscape of TNBC has encouraged the exploration of drugs that interfere with the DNA repair mechanism and that modulate immune response. Overall, these drugs seem to improve the pCR rate in TNBC, despite preliminary and heterogeneous results. Taking into account the economic issues and the side effects of these drugs, it is crucial to further explore the potential predictive role of BRCA mutational status and homologous recombination deficiency score, for platinum agents and PARP-inhibitors, and tumor infiltrating lymphocytes and other immune biomarkers for checkpoint inhibitors, respectively.

摘要

简介

尽管三阴性乳腺癌(TNBC)的分子特征在最近取得了进展,但早期 TNBC 的标准治疗仍然是历史上使用的蒽环类和紫杉烷类化疗。在精准医学的现代时代,已经在 TNBC 的新辅助治疗中研究了几种新的治疗策略和新型药物,以实现个体化治疗。

涵盖领域

本文综述了目前关于铂类药物、PARP 和免疫检查点抑制剂在 TNBC 新辅助治疗中的活性和疗效的可用证据,强调了关于这些治疗反应或耐药的潜在预测生物标志物的可用数据。

专家意见

TNBC 的基因组和免疫景观鼓励探索干扰 DNA 修复机制和调节免疫反应的药物。总的来说,这些药物似乎提高了 TNBC 的 pCR 率,尽管初步结果存在差异。考虑到这些药物的经济问题和副作用,探索 BRCA 突变状态和同源重组缺陷评分对铂类药物和 PARP 抑制剂的潜在预测作用,以及肿瘤浸润淋巴细胞和其他免疫生物标志物对检查点抑制剂的潜在预测作用至关重要。

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