Supplementary Material for: Trastuzumab deruxtecan for HER2-positive breast cancer with central nervous system metastasis

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 40s. 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 40s 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.

引言：中枢神经系统（CNS）转移在人类表皮生长因子受体（HER2）阳性乳腺癌中较为常见，导致生活质量下降及预后不佳。脑转移（BM）较为普遍，而脊髓转移则较为罕见，且目前尚无针对其管理的标准化治疗方案。本研究报道了两位患者接受曲妥珠单抗衍生物T-DXd（trastuzumab deruxtecan）治疗脑转移（BM）及脊髓内转移（ISCM）的疗效。案例报告：第一位患者为40岁女性，在完成HER2阳性右侧乳腺癌手术治疗后，T-DXd作为第四线治疗用于多发性BM和ISCM。BM和ISCM均有所缩小，且在12个月内维持了部分缓解。本患者仅观察到1级疲劳作为不良事件。第二位患者为40岁女性，在完成HER2阳性右侧乳腺癌的初治后，出现了多发性BM以及多发性骨和淋巴节点转移。T-DXd作为第二线治疗被给予。目前，多发性BM已缩小，而原发肿瘤及骨/淋巴节点转移未见显著变化；患者在6个月内维持了部分缓解。结论：中枢神经系统转移的预后极差，且治疗反应有限，因为药物难以穿过血脑屏障。然而，T-DXd在临床试验中对BM的疗效已得到证实。此外，在所报道的案例中，T-DXd对ISCM和BM的治疗效果也得到了观察。