Department of Medical Oncology, IRCCS Ospedale San Raffaele, Milan, Italy.
Università Vita-Salute San Raffaele, Milan, Italy.
Nat Rev Clin Oncol. 2022 Feb;19(2):91-113. doi: 10.1038/s41571-021-00565-2. Epub 2021 Nov 9.
Tumour heterogeneity and a long-standing paucity of effective therapies other than chemotherapy have contributed to triple-negative breast cancer (TNBC) being the subtype with the least favourable outcomes. In the past few years, advances in omics technologies have shed light on the relevance of the TNBC microenvironment heterogeneity, unveiling a close dynamic relationship with cancer cell features. An improved understanding of tumour-immune system co-evolution supports the need to adopt a more comprehensive view of TNBC as an ecosystem that encompasses the intrinsic and extrinsic features of cancer cells. This new appreciation of the biology of TNBC has already led to the development of novel targeted agents, including PARP inhibitors, antibody-drug conjugates and immune-checkpoint inhibitors, which are revolutionizing the therapeutic landscape and providing new opportunities both for patients with early-stage TNBC and for those with advanced-stage disease. The current therapeutic scenario is only the tip of the iceberg, as hundreds of new compounds and combinations are in development. The translation of these experimental therapies into clinical benefit is a welcome and ongoing challenge. In this Review, we describe the current and upcoming therapeutic landscape of TNBC and discuss how an integrated view of the TNBC ecosystem can define different levels of risk and provide improved opportunities for tailoring treatment.
肿瘤异质性以及除化疗以外缺乏有效的治疗方法,导致三阴性乳腺癌(TNBC)成为预后最差的亚型。在过去几年中,组学技术的进步揭示了 TNBC 微环境异质性的相关性,揭示了与癌细胞特征的密切动态关系。对肿瘤-免疫系统共同进化的深入了解支持了需要采用更全面的观点来认识 TNBC,将其视为一个包含癌细胞内在和外在特征的生态系统。对 TNBC 生物学的这种新认识已经导致了新型靶向药物的开发,包括 PARP 抑制剂、抗体药物偶联物和免疫检查点抑制剂,这些药物正在彻底改变治疗格局,并为早期 TNBC 患者和晚期疾病患者提供新的机会。目前的治疗情况只是冰山一角,因为有数百种新的化合物和组合正在开发中。将这些实验性治疗转化为临床获益是一个受欢迎且正在进行的挑战。在这篇综述中,我们描述了 TNBC 的当前和即将到来的治疗前景,并讨论了如何通过对 TNBC 生态系统的综合观点来定义不同的风险水平,并为定制治疗提供更好的机会。