Supplementary Material for: Excellent response to trastuzumab deruxutecan of a large medullary metastasis from HER2-positive breast cancer: A case report

Introduction: Brain metastasis is a serious complication in human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Brainstem metastases are particularly challenging to treat because of the high risks associated with surgery and stereotactic radiosurgery. Case Presentation: We present a case of a 56-year-old woman with HER2-positive breast cancer who developed multiple brain metastases, including a large medullary lesion, 9 months after surgery confirming a pathological complete response to standard trastuzumab plus pertuzumab-based neo-adjuvant chemotherapy, without extra-cranial lesions. Surgery was deemed infeasible because the lesion’s location and size posed high risks of toxicity from stereotactic radiosurgery. Promising intra-cranial responses to trastuzumab deruxutecan (T-DXd) have been reported; therefore, T-DXd was chosen. Remarkable symptomatic improvements were observed within days after initiating T-DXd. Imaging confirmed radiographic responses and metabolic response indicated by the absence of uptake of 11C‐methionine on positron emission tomography-computed tomography. No evidence of relapse has been observed after the 14 months since the initiation of T-DXd. Conclusion: This case indicates the efficacy of T-DXd in treating large medullary metastases, achieving rapid and sustained responses even in high-risk situations where conventional therapies may not be suitable. Furthermore, the fact that the brain metastases occurred after pathological complete response without extra-cranial lesions may indicate the superiority of T-DXd over conventional anti-HER2 antibodies for brain metastasis. This case underscores the potential of T-DXd as a viable treatment option for brain metastases. Further studies are required to establish its safety and efficacy in similar high-risk scenarios.