A Dramatic Clinical Response to Trastuzumab-Deruxtecan in a Patient with HER-2 Low Breast Cancer with Untreated Leptomeningeal Metastasis and Hydrocephalus

Leptomeningeal metastasis (LM) is a rare and challenging manifestation of advanced breast cancer (ABC) with severe morbidity and mortality. Patients with LM may be asymptomatic, or present with non-specific neurologic deficits, thereby possibly delaying diagnosis. Treatment typically requires a multimodal approach for effective management, symptom relief, and quality-of-life improvement. Trastuzumab-deruxtecan (T-DXd), a humanized monoclonal antibody drug conjugate, demonstrated efficacy across diverse breast cancer subtypes expressing variable levels of HER2 proteins. Currently, T-DXd is the standard of care for patients with advanced, pretreated, HER2 low breast cancer. There is limited evidence of the response of brain metastases (BM) and leptomeningeal metastases (LM) to T-DXd in HER2-low patients, with most data extrapolated from HER2-positive breast cancer studies. This case report presents the first documented instance of a patient with debilitating, symptomatic, untreated LM and hydrocephalus demonstrating a rapid and dramatic clinical response to T-DXd. This finding holds crucial clinical relevance, highlighting the potential benefit of initiating effective systemic therapy for LM early in treatment to address both central nervous system (CNS) and non-CNS disease burden, rather than delaying systemic therapy until after radiation therapy.