Pinilla Karen, Drewett Lynsey M, Lucey Rebecca, Abraham Jean E
Precision Breast Cancer Institute, University of Cambridge, Cambridge, United Kingdom.
Department of Oncology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom.
Front Oncol. 2022 Aug 8;12:866889. doi: 10.3389/fonc.2022.866889. eCollection 2022.
Personalised approaches to the management of all solid tumours are increasing rapidly, along with wider accessibility for clinicians. Advances in tumour characterisation and targeted therapies have placed triple-negative breast cancers (TNBC) at the forefront of this approach. TNBC is a highly heterogeneous disease with various histopathological features and is driven by distinct molecular alterations. The ability to tailor individualised and effective treatments for each patient is of particular importance in this group due to the high risk of distant recurrence and death. The mainstay of treatment across all subtypes of TNBC has historically been cytotoxic chemotherapy, which is often associated with off-target tissue toxicity and drug resistance. Neoadjuvant chemotherapy is commonly used as it allows close monitoring of early treatment response and provides valuable prognostic information. Patients who achieve a complete pathological response after neoadjuvant chemotherapy are known to have significantly improved long-term outcomes. Conversely, poor responders face a higher risk of relapse and death. The identification of those subgroups that are more likely to benefit from breakthroughs in the personalised approach is a challenge of the current era where several targeted therapies are available. This review presents an overview of contemporary practice, and promising future trends in the management of early TNBC. Platinum chemotherapy, DNA damage response (DDR) inhibitors, immune checkpoint inhibitors, inhibitors of the PI3K-AKT-mTOR, and androgen receptor (AR) pathways are some of the increasingly studied therapies which will be reviewed. We will also discuss the growing evidence for less-developed agents and predictive biomarkers that are likely to contribute to the forthcoming advances in this field. Finally, we will propose a framework for the personalised management of TNBC based upon the integration of clinico-pathological and molecular features to ensure that long-term outcomes are optimised.
随着临床医生对个性化方法的可及性提高，针对所有实体瘤的个性化管理方法正在迅速增加。肿瘤特征分析和靶向治疗的进展使三阴性乳腺癌（TNBC）处于这种方法的前沿。TNBC是一种高度异质性疾病，具有多种组织病理学特征，并由不同的分子改变驱动。由于远处复发和死亡风险高，为每位患者量身定制个体化有效治疗的能力在这一群体中尤为重要。历史上，TNBC所有亚型的主要治疗方法一直是细胞毒性化疗，这通常与非靶向组织毒性和耐药性相关。新辅助化疗常用，因为它允许密切监测早期治疗反应并提供有价值的预后信息。已知在新辅助化疗后实现完全病理缓解的患者长期预后有显著改善。相反，反应不佳的患者面临更高的复发和死亡风险。在当前有几种靶向治疗可用的时代，识别那些更可能从个性化方法突破中受益的亚组是一项挑战。本综述概述了早期TNBC管理的当代实践和有前景的未来趋势。铂类化疗、DNA损伤反应（DDR）抑制剂、免疫检查点抑制剂、PI3K-AKT-mTOR抑制剂和雄激素受体（AR）途径是一些越来越受研究的疗法，将在本文中进行综述。我们还将讨论一些研究较少的药物和预测生物标志物的越来越多的证据，这些可能有助于该领域即将取得的进展。最后，我们将基于临床病理和分子特征的整合提出一个TNBC个性化管理框架，以确保优化长期预后。
