Abstract P1-10-19: Hypophysitis and Haziness in HER2: A Case of Breast Cancer with Leptomeningeal Carcinomatosis

Abstract Background: HER2 is overexpressed in up to 30% of breast cancers. These patients have increased risk for development of CNS metastases, including leptomeningeal carcinomatosis despite use of HER2 targeted therapy. Historically the development of leptomeningeal disease has carried a poor prognosis, with studies showing overall survival of 3 to 4 months. Case Presentation: 41-year-old female with Lynch syndrome originally presented to an outside facility with ER+/HER2+ de novo breast cancer metastatic to liver and brain treated with trastuzumab, pertuzumab, and weekly paclitaxel for one year. There was no evidence of disease on follow-up imaging. Following TAH/BSO, she started daily anastrozole and continued this for 2 years. She presented 2 years later with multiple metastatic brain lesions. She underwent definitive stereotactic radiosurgery (SRS) and was enrolled in a clinical trial using pembrolizumab for 3 cycles following SRS treatment. She presented to our institution 3 months after SRS with fatigue, nausea/vomiting, left eye blurred vision and mydriasis. MRI imaging of the brain showed changes consistent with leptomeningeal carcinomatosis and thickening of the infundibulum, consistent with hypophysitis. CSF cytology revealed abnormal appearing cells, suspicious for mammary carcinoma. Abdominal imaging showed rapid development of numerous hepatic metastases not observed on abdominal imaging two weeks prior. Liver biopsy revealed HER2+ (3+) metastatic breast cancer. She began systemic and intrathecal (IT) trastuzumab, in addition to capecitabine and tucatinib per HER2 CLIMB. IT trastuzumab was given 80mg twice weekly for 4 weeks, followed by once weekly for 4 weeks, followed by 80mg every 2 weeks thereafter. Hypophysitis was treated with steroids. Follow-up after 4 cycles of systemic and IT treatment revealed clinical improvement with return of vision in left eye; imaging showed improvement in leptomeningeal and hepatic disease burden. Most recent imaging seven months after initiation of current treatment course showed stable leptomeningial disease, no abnormal cells in the CSF and improved systemic disease. Nine months following initiation of therapy she remains with stable symptoms. Conclusion: As demonstrated in this case, treatment of HER2+ breast cancer with leptomeningeal metastases with intrathecal trastuzumab can extend survival above historically reported data, with limited toxicity. Citation Format: Caitlin Sullivan, Nali Gillespie, Brian Boulmay, Rajasree Chowdry, Jonathan Somma, Agustin Garcia, Michelle Loch. Hypophysitis and Haziness in HER2: A Case of Breast Cancer with Leptomeningeal Carcinomatosis [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P1-10-19.