Dr. Balaji Jegannathan*¹, Dr. Raja Gopal², Dr. Senthilkumar Elumalai³, Dr. Anusha Tummula⁴

¹The Tamil Nadu Dr. M.G.R. Medical University, 69, Anna Salai, Little Mount, Guindy, Chennai, Tamil Nadu 600032, Email: oncobalaji@gmail.com

²The Tamil Nadu Dr. M.G.R. Medical University, 69, Anna Salai, Little Mount, Guindy, Chennai, Tamil Nadu 600032, Email: grajaro78@gmail.com

³The Tamil Nadu Dr. M.G.R. Medical University, 69, Anna Salai, Little Mount, Guindy, Chennai, Tamil Nadu 600032, Email: esenthilkmc02@gmail.com

⁴The Tamil Nadu Dr. M.G.R. Medical University, 69, Anna Salai, Little Mount, Guindy, Chennai, Tamil Nadu 600032, Email: tummala3333@gmail.com

Corresponding Author: Dr. Balaji Jegannathan, The Tamil Nadu Dr. M.G.R. Medical University, 69, Anna Salai, Little Mount, Guindy, Chennai, Tamil Nadu 600032, Email: oncobalaji@gmail.com.

Citation: Dr. Balaji Jegannathan, Dr. Raja Gopal, Dr. Senthilkumar Elumalai, Dr. Anusha Tummula (2026) Solitary Intracranial Progression on Trastuzumab Deruxtecan Therapy in HER2-Positive Metastatic Breast Cancer: A Case Report. World J Case Rep Clin Imag. 2026 October; 5(2),1-5.

Copyrights © Dr. Balaji Jegannathan, et al., 2026, This article is licensed under the Creative Commons Attribution-NonCommercial-4.0-International-License-(CCBY-NC) (https://worldjournalofcasereports.org/blogpage/copyright-policy). Usage and distribution for commercial purposes require written permission.

Abstract:

Background: Human epidermal growth factor receptor 2 (HER2)-positive breast cancer is characterized by a substantial risk of central nervous system (CNS) metastases. However newer agents such as Trastuzumab deruxtecan (T-DXd) has demonstrated substantial systemic efficacy and clinically meaningful intracranial activity in these patients. Nevertheless, CNS progression can occur despite excellent extracranial disease control even whilst on these agents.

Case presentation: We report the case of a 52-year-old postmenopausal woman with locally advanced, HER2-positive invasive ductal carcinoma of the left breast (cT3N1M0, HER2 3+, HER2-enriched phenotype). She received neoadjuvant docetaxel, carboplatin, trastuzumab, and pertuzumab, followed by left modified radical mastectomy, with residual ypT1bN1a disease. After completion of one year of adjuvant trastuzumab, she remained disease-free until March 2025, when imaging demonstrated widespread metastatic disease involving the lungs, liver, mediastinal and supraclavicular lymph nodes, bone, and a sellar-suprasellar lesion. After intolerance to one cycle of trastuzumab emtansine (T-DM1), multidisciplinary review led to stereotactic radiotherapy to the intracranial lesions followed by systemic T-DXd.

She subsequently received T-DXd with marked systemic response. After six cycles, positron emission tomography-computed tomography (PET-CT) demonstrated a complete metabolic response in the suprasellar lesion and extensive extracranial metastatic sites, with only a small non-FDG-avid pulmonary scar and complete resolution of liver lesions. T-DXd was continued for four additional cycles. However, approximately the following period was characterized by new multifocal intracranial enhancing lesions involving the cerebellum, brainstem, cerebral hemispheres, and thalamus, with subsequent PET-CT demonstrating diffuse leptomeningeal metastatic disease. The patient was subsequently switched to tucatinib, trastuzumab, and capecitabine.

Conclusion: This case illustrates the potential for discordant CNS and extracranial responses during T-DXd therapy. Of particular interest is the development of limited intracranial progression despite a profound systemic response, followed by diffuse CNS/leptomeningeal dissemination. The case underscores the importance of continued CNS surveillance in HER2-positive metastatic breast cancer, even when systemic disease remains in complete metabolic response, and highlights the clinical challenge of CNS sanctuary disease during highly effective HER2-directed therapy.

Keywords: HER2-positive Breast Cancer, Trastuzumab Deruxtecan, T-DXD, Brain Metastasis, Intracranial Progression, Leptomeningeal Metastasis, CNS Sanctuary Disease, Sellar Metastasis, Stereotactic Radiotherapy.