O'Meara Tess A, Tarantino Paolo, Morganti Stefania, Schlam Ilana, Garrido-Castro Ana C, Tolaney Sara M
Susan F. Smith Center for Women's Cancers, Breast Oncology Program, Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA.
Curr Oncol Rep. 2025 Jan;27(1):68-79. doi: 10.1007/s11912-024-01628-0. Epub 2025 Jan 5.
In this review, we discuss evidence supporting the use of antibody-drug conjugates (ADCs) in breast cancer treatment, describe novel ADCs and combination regimens under development, and examine our current understanding of resistance mechanisms and biomarkers to guide ADC selection and sequencing.
Three ADCs have proven benefit in patients with metastatic breast cancer: trastuzumab emtansine (T-DM1), trastuzumab deruxtecan (T-DXd), and sacituzumab govitecan (SG). There are over two hundred investigational ADCs on the horizon, as pre-clinical studies work to identify novel ADC targets and structures. In this new frontier, translational efforts are underway to personalize the use of ADCs, including refining HER2 quantification and elucidating genetic, epigenetic, and post-translational mechanisms of resistance. ADCs have provided important treatment options for patients with breast cancer. As patients become eligible for more than one ADC, there is an unmet need to identify the appropriate timing and sequence of these therapies to maximize their efficacy.
在本综述中，我们讨论支持抗体药物偶联物（ADC）用于乳腺癌治疗的证据，描述正在研发的新型ADC和联合治疗方案，并审视我们目前对耐药机制和生物标志物的理解，以指导ADC的选择和排序。
三种ADC已被证明对转移性乳腺癌患者有益：曲妥珠单抗 emtansine（T-DM1）、曲妥珠单抗 deruxtecan（T-DXd）和戈沙妥珠单抗（SG）。随着临床前研究致力于确定新的ADC靶点和结构，即将有超过两百种研究性ADC问世。在这个新领域，正在进行转化研究以实现ADC的个性化使用，包括完善HER2定量以及阐明耐药的遗传、表观遗传和翻译后机制。ADC为乳腺癌患者提供了重要的治疗选择。随着患者有资格使用不止一种ADC，确定这些治疗的合适时机和顺序以最大化其疗效的需求尚未得到满足。
