Supplementary Material for: Response of brain and meningeal metastases to trastuzumab-deruxtecan in a patient with HER2-low breast cancer

Introduction: nervous system metastases (CNSm) are late events associated with poor outcomes in endocrine-sensitive HER2-negative breast cancer (BC) patients, especially in the presence of leptomeningeal disease (LMD). Effective treatments are extremely limited in this setting. The antibody-drug conjugate, trastuzumab-deruxtecan (T-DXd), which combines the anti-HER2 antibody trastuzumab with a topoisomerase type 1 inhibitor, showed high efficacy not only against HER2-positive, but also HER2-low metastatic breast cancers (BC), expressing HER2 at a lower level. Case presentation: To the best of our knowledge, this is the first report of a patient with metastatic endocrine-sensitive HER2-low BC suffering from BMs associated with LMD and sustained disease control when treated with T-DXd. Conclusion: Several recent case series have reported the activity of T-DXd in patients with HER2-positive disease and brain metastases (BMs) or leptomeningeal disease (LMD), but none in HER2-low patients. This case is particularly relevant since more than 50% of BCs are HER2-low.