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Review
. 2025 Mar 20;14(1):41.
doi: 10.1186/s40164-025-00632-9.

Antibody-drug conjugates in breast cancer: current evidence and future directions

Ning Li #  1 , Lu Yang #  2   3 , Zixuan Zhao #  1 , Tian Du  1 , Gehao Liang  1 , Na Li  4 , Jun Tang  5
Affiliations
Review

Antibody-drug conjugates in breast cancer: current evidence and future directions

Ning Li et al. Exp Hematol Oncol. .

Abstract

Antibody-drug conjugates (ADCs) are a rapidly evolving class of antitumor drugs and have already revolutionized the treatment strategy of many hematologic and solid cancers. So far, trastuzumab emtansine (T-DM1), trastuzumab deruxtecan (T-DXd), sacituzumab govitecan (SG) and datopotamab deruxtecan (Dato-DXd) are the four ADCs that have been approved by US food and drug administration (FDA) in treatment of breast cancer, and SKB264 has been approved by Chinese national medical products administration (NMPA). Many ADCs for treatment of breast cancer are currently being tested in late-phase clinical trials, with several encouraging results achieved recently. However, major issues arise during the use of ADCs, including emergence of acquired resistance, occurrence of treated-related toxicities, and identification of biomarkers of response and resistance. ADCs are being increasingly tested in combination with other agents, and novel next-generation ADC development is progressing rapidly. A better understanding of the design and development of ADCs will promote ADC development for cancer treatment. In this review, we aim to provide a broad overview of the design and the recent advances of ADCs in breast cancer. We also propose several notable future directions of ADCs in treatment of breast cancer.

Keywords: Antibody-drug conjugate; Biomarker; Breast cancer; Combination therapy; Trials.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: All authors have agreed to publish the present work in its submitted form. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Structure and mechanisms of action of an ADC (A) Structure of a conventional ADC; (B) Mechanisms of action of a conventional ADC. ADC, antibody-drug conjugate; DAR, drug-to-antibody ratio; IgG, immunoglobulin G. Created in BioRender. Li, N. (2025) https://BioRender.com/a67b702
Fig. 2
Fig. 2
Timeline showing the approval of ADCs in breast cancer. Data cutoff date, January 31, 2025. T-DM1, trastuzumab emtansine; T-DXd, trastuzumab deruxtecan; SG, sacituzumab govitecan; Dato-DXd, datopotamab deruxtecan; HER2, human epidermal growth factor receptor 2; HR, hormone receptor; TNBC, triple-negative breast cancer; NMPA, national medical products administration; -/+, negative/positive
Fig. 3
Fig. 3
Pivotal clinical trials of ADCs in breast cancer according to different agents and treatment settings. Data cutoff date, January 31, 2025. T-DM1, trastuzumab emtansine; T-DXd, trastuzumab deruxtecan; SG, sacituzumab govitecan; Dato-DXd, datopotamab deruxtecan; P, pertuzumab; TCbHP, docetaxel-carboplatin-trastuzumab-pertuzumab; H, trastuzumab; THP, taxane-trastuzumab-pertuzumab, TH, paclitaxel-trastuzumab; SOC, standard of care; TPC, treatment of physician’s choice; Ana, anastrozole; Ate, atezolizumab; AC, anthracycline-cyclophosphamide; Pem, pembrolizumab; Dur, durvalumab
Fig. 4
Fig. 4
Future directions of ADCs in breast cancer. ADC, antibody–drug conjugate; HER2, human epidermal growth factor receptor 2; TROP2, trophoblast cell surface antigen-2; ILD, interstitial lung disease; PD-(L)1, programmed death-1/programmed death-ligand 1. Created in BioRender. Li, N. (2025) https://BioRender.com/t70c288
See this image and copyright information in PMC

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