INTRODUCTION: Metastasis to the central nervous system (CNS) is frequently observed in human epidermal growth factor receptor (HER2)-positive breast cancer, leading to reduced quality of life and poor prognosis. Brain metastases (BMs) are common, whereas spinal cord metastases are rare and no standardized treatment approach has been reported for their management. Herein, we report the outcomes of treatment with trastuzumab deruxtecan (T-DXd) in a patient with BMs and intramedullary spinal cord metastasis (ISCM) and another patient with BMs. CASE PRESENTATION: The first patient was a woman in her 30s. After the surgery for HER2-positive right breast cancer, T-DXd was used as fourth-line treatment for multiple BMs and ISCM. Both the BMs and ISCM reduced, and partial response was maintained for 12 months. Grade 1 fatigue was the only adverse event observed in this patient. The second patient was a woman in her 40 s with multiple BMs after primary treatment for HER2-positive right breast cancer, as well as multiple bone and lymphoid node metastases. T-DXd was administered as second-line treatment. The multiple BMs have now shrunk, and the primary tumor and bone/lymph node metastases have not shown significant changes
the patient has maintained partial response for 6 months. CONCLUSION: Metastasis to the CNS has a very poor prognosis and limited therapeutic response because it is difficult for drugs to cross the blood-brain barrier. However, T-DXd has yielded positive results for BMs in clinical trials. Additionally, a therapeutic effect of T-DXd on ISCM and BMs was observed in the reported cases.