Introduction

Advanced breast cancer (ABC) is a leading cause of mortality, morbidity, and disability in women worldwide. For decades, treatment of ABC has relied on chemotherapy and endocrine treatments (ET), until HER2 was recognized as a ‘druggable’ target in the 1990s. Thereafter, various anti-HER2 drugs have been approved for the HER2-positive subtype, but only in the last few years, biologic agents targeting different pathways have entered the therapeutic arsenal of luminal and triple-negative cancers.

Areas covered

The purpose of the present review is to recapitulate the most promising novel biologic agents being developed for the treatment of ABC. New drugs for all breast cancer subtypes are discussed, as well as some potential future directions in ABC treatment.

Expert opinion

Several biologic drugs have been recently approved, revolutionizing ABC treatment algorithms: key examples are CDK4/6-inhibitors and the PI3K-inhibitor alpelisib for endocrine-positive ABC; atezolizumab for triple-negative cancers; two PARP-inhibitors for HER2-negative germinal BRCA-mutated cancers. Additionally, multiple drugs are demonstrating activity in late-phase clinical trials for all subtypes. While some of these represent pharmacological evolutions of previously approved drugs, some others might pave the way for new paradigms in ABC, challenging both its classification and current treatment algorithms.

中文翻译：

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晚期乳腺癌的生物疗法：最新进展和未来方向。

介绍

晚期乳腺癌（ABC）是导致全球女性死亡，发病和致残的主要原因。几十年来，ABC的治疗一直依靠化学疗法和内分泌治疗（ET），直到HER2在1990年代被公认为是“可消耗的”靶标。此后，已针对HER2阳性亚型批准了各种抗HER2药物，但仅在最近几年中，针对不同途径的生物制剂才进入管腔和三阴性癌症的治疗库。

覆盖区域

本综述的目的是概述正在开发用于治疗ABC的最有希望的新型生物制剂。讨论了所有乳腺癌亚型的新药，以及ABC治疗的一些潜在的未来方向。

专家意见

最近已批准了几种生物药物，彻底改变了ABC治疗算法：关键示例是内分泌阳性ABC的CDK4 / 6抑制剂和PI3K抑制剂alpelisib。Atezolizumab用于三阴性癌症；HER2阴性生发性BRCA突变癌症的两种PARP抑制剂。此外，在所有亚型的晚期临床试验中，多种药物均显示出活性。尽管其中一些代表先前批准药物的药理学演变，但另一些可能为ABC中的新范式铺平了道路，同时挑战了其分类和当前的治疗算法。