Trastuzumab deruxtecan in HER2-positive metastatic breast cancer with severe hepatic dysfunction: a case report and narrative literature review.

Trastuzumab deruxtecan (T-DXd) has transformed the management of Human Epidermal Growth Factor Receptor 2 (HER2)-positive metastatic breast cancer (mBC). However, its role in visceral crisis (VC) remains unclear due to exclusion from clinical trials and limited real-world evidence. We report the case of a 40-year-old woman with HER2-positive mBC who after first-line therapy developed severe hepatic dysfunction due to liver progression, consistent with hepatic VC. Following multidisciplinary discussion and informed consent, T-DXd as second line therapy was initiated at a reduced dose (3.2 mg/kg), leading to rapid normalization of liver function, symptom relief, and radiologic response. Subsequent stepwise escalation to the standard dose (5.4 mg/kg) was well tolerated, with durable disease control and no additional toxicity. Our findings, in this otherwise underexplored setting, together with similar experiences reported in the literature, support T-DXd as a safe and effective therapeutic option for HER2-positive mBC complicated by hepatic VC. Further evidence is needed to better inform clinical practice in terms of optimal, tailored dose-escalation strategies in this context.