Objective  Using the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database to analyze post-marketing adverse drug event (ADE) risk signals of three antibody-drug conjugates (ADCs)—trastuzumab emtansine, trastuzumab deruxtecan, and sacituzumab govitecan—for breast cancer, and to provide references for safe clinical medication.

Methods  Reports were retrieved from the FAERS database from Q1 2004 to Q1 2025, extracting primary suspected drug reports for three ADC drugs. Signal detection was performed using report odds ratio and the proportion of reports ratio. Signals were screened, and the distribution of system organ classes (SOCs) and severe outcomes were analyzed.

Results  A total of 7,620 ADE reports were included, 2,786 for trastuzumab emtansine,  3,705 for trastuzumab deruxtecan,  and 1,129 for sacituzumab govitecan. The proportions of death outcomes were 15.83%, 22.29%, and 18.42%, respectively. Three drugs exhibited significant risk signals in the hepatobiliary, respiratory, and gastrointestinal systems, respectively. Certain signals—such as subcapsular hepatic hematoma, Pneumocystis jirovecii pneumonia, and necrotizing colitis—were not explicitly highlighted in the product labeling. A total of 14 SOCs and 40 preferred terms were identified as new ADE signals.

Conclusion  Three ADCs exhibite multisystem ADE signals in breast cancer populations, with some risk indicators remaining insufficiently characterize. Clinicians should enhance recognition and monitoring of severe ADEs associated with ADC drugs, particularly in immunocompromised patients, those receiving multiple lines of therapy, or individuals with comorbidities. This study provides real-world evidence to optimize clinical management strategies for ADC drugs.

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