PS5-06-18: Paraneoplastic Encephalitis in Breast Cancer

Abstract Introduction Paraneoplastic Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is one of the most common types of immune-mediated encephalitis characterized by the collection of immune-mediated nervous system symptoms that arise due to malignancy1,2. However, NMDAR encephalitis is a rare manifestation of breast cancer. We present the case of a 31-year-old female with progressive neurological decline due to paraneoplastic encephalitis with a subsequent breast cancer diagnosis. Treatment with tamoxifen led to significant improvement, emphasizing the importance of identifying underlying etiology and treatment of NMDA encephalitis for improved outcomes. Patient Presentation A 31-year-old female presented with an 11-month history of progressive neurological decline characterized by confusion, psychosis, dysarthria, severe ataxia requiring a walker, amnesia, aggression, violence, and insomnia. Subsequently, she experienced progressive dysphagia and dysarthria resulting in an inability to speak beyond grunts. She was admitted to the psychiatric unit 3 times during this 11-month period. Clinical CourseThe patient was admitted to the Neurology floor and then transferred to Neuro ICU on day 2 of hospitalization due to hypoxic respiratory failure due to fluctuating mental status with associated bradytachycardia, diffuse rigidity, and agitation She underwent tracheostomy and PEG placement. Diagnostic testing demonstrated leukocytosis, anemia, thrombocytopenia, hyperglycemia, +ANA, elevated CRP 21.5 and ESR 40, +SSA, elevated CK, low TSH 0.123, SPEP with diffuse hypergammaglobulinemia. Encephalitis antibody panel was positive for AMPA receptor Ab. Lumbar puncture (LP) was unremarkable, and EEG showed activity consistent with mild encephalopathy. MRI brain demonstrated hyperintense areas in bilateral frontal, parietal, and right temporal lobe suggestive of autoimmune encephalitis. Treatment for neurologic symptoms included methylprednisolone daily and IVIG for 5 days, followed by 7 sessions of therapeutic plasmapheresis. Psychiatry was consulted, and she underwent six sessions of ECT, initiated on Ativan, and transitioned to Thorazine twice daily. CT chest showed right axillary adenopathy without evidence of distant disease. Right axillary biopsy confirmed invasive carcinoma, consistent with breast primary, ER+, PR+. HER2 2+, FISH not amplified, Ki-67 20-30%. She was started on Tamoxifen with gradual improvement in her symptoms. Patient was discharged from hospital and regained complete neuromechanical function after about three months of single agent Tamoxifen. She was transitioned to neoadjuvant dose-dense Adriamycin and Cyclophosphamide followed by Paclitaxel with plan to undergo surgical resection. Conclusion Paraneoplastic encephalitis is a rare diagnosis in breast cancer, reported in less than 1% of patient’s with breast cancer. AMPA-R encephalitis is a paraneoplastic syndrome associated with breast cancer caused by onconeural antibodies directed against cancer cells, resulting in inflammation and injury to limbic strictures in the brain. This case highlights the importance of a thorough assessment in the evaluation of unexplained neurologic and psychological decline which includes imaging, LP, antibody testing, EEG, and biopsy. It also stresses the importance of identifying and treating the underlying malignancy which may result in resolution of symptoms. Citation Format: C. Onyeukwu, M. Boamah, J. Steffes, N. Dhliwayo, S. Lo, T. Christ. Paraneoplastic Encephalitis in Breast Cancer abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-06-18.