European Institute of Oncology, IRCCS, Division of Early Drug Development for Innovative Therapies , Milan, Italy.
Department of Oncology and Hemato-Oncology, University of Milan , Milan, Italy.
Expert Opin Biol Ther. 2020 Sep;20(9):1009-1024. doi: 10.1080/14712598.2020.1752176. Epub 2020 Apr 21.
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.
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.
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.
晚期乳腺癌（ABC）是全球女性死亡、发病和残疾的主要原因。几十年来，ABC 的治疗一直依赖于化疗和内分泌治疗（ET），直到 20 世纪 90 年代 HER2 被确认为“可靶向治疗”靶点。此后，各种抗 HER2 药物已被批准用于 HER2 阳性亚型，但直到最近几年，针对不同途径的生物制剂才进入了 luminal 和三阴性癌症的治疗武器库。
本综述的目的是总结目前正在开发用于治疗 ABC 的最有前途的新型生物制剂。讨论了适用于所有乳腺癌亚型的新药，以及 ABC 治疗的一些潜在未来方向。
最近批准了几种生物药物，彻底改变了 ABC 的治疗方案：关键例子是 CDK4/6 抑制剂和内分泌阳性 ABC 的 PI3K 抑制剂 alpelisib；atezolizumab 用于三阴性癌症；两种 PARP 抑制剂用于 HER2 阴性生殖系 BRCA 突变癌症。此外，多种药物在所有亚型的后期临床试验中均显示出活性。虽然其中一些代表了以前批准药物的药理学进展，但另一些可能为 ABC 开辟新的范例，挑战其分类和当前的治疗方案。
