European Organization for Research and Treatment of Cancer (EORTC) Headquarters, Brussels, Belgium.
Breast International Group (BIG), Brussels, Belgium.
Cancer Treat Rev. 2016 Nov;50:68-81. doi: 10.1016/j.ctrv.2016.08.008. Epub 2016 Sep 7.
Hormone receptor positive breast cancer (HR-positive BC) is the most frequent BC subtype (∼70%), with endocrine treatment constituting its therapeutic cornerstone; despite its efficacy, endocrine resistance can develop, clinically as a relapse or a progression of the early or advanced disease respectively, hence necessitating alternative treatments. Over the last two decades, improved understanding of the molecular mechanisms of endocrine resistance has been achieved, with numerous targeted agents undergoing clinical development. Despite the multifactorial genesis of endocrine resistance, fuelled not only by alternative oncogenic signaling pathways of tumor cells, but also by tumor microenvironment-mediated mechanisms, successful clinical development of new agents has been recently noted. However, predictive biomarkers for accurate 'navigation' across the different treatment options are urgently needed. In this article, we present a thorough overview of the different clinical scenarios of BC endocrine resistance, and the recent advances in endocrine treatment, we describe the basic molecular mediators of endocrine resistance and the respective targeted agents undergoing clinical development; finally, we provide our perspective on the future of BC endocrine treatment.
激素受体阳性乳腺癌（HR 阳性 BC）是最常见的乳腺癌亚型（~70%），内分泌治疗是其治疗基石；尽管有效，但可能会发生内分泌耐药，临床上分别表现为复发或早期或晚期疾病的进展，因此需要替代治疗。在过去的二十年中，人们对内分泌耐药的分子机制有了更深入的了解，许多靶向药物正在进行临床开发。尽管内分泌耐药的发生是多因素的，不仅受到肿瘤细胞的替代致癌信号通路的驱动，还受到肿瘤微环境介导的机制的驱动，但最近已经注意到新药物的成功临床开发。然而，迫切需要用于准确“导航”不同治疗选择的预测生物标志物。在本文中，我们全面概述了 BC 内分泌耐药的不同临床情况以及内分泌治疗的最新进展，我们描述了内分泌耐药的基本分子介质和正在进行临床开发的相应靶向药物；最后，我们对 BC 内分泌治疗的未来提出了看法。
