Antibody-Drug Conjugates in Breast Cancer: The Road Towards Biologically-Informed Selection and Sequencing.

Abstract

Purpose of review: 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.

Recent findings: 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.