Abstract PS5-02-04: Incidence of the development of brain metastases in patients with advanced stage HER2+ breast cancer who have previously received a HER2 directed cancer vaccine

Abstract Background: HER2-positive breast cancer, characterized by the overexpression of the HER2 protein, has been associated with an aggressive disease course, higher rates of recurrence, and poorer prognosis compared to HER2-negative breast cancer and accounts for approximately 15-20% of all breast cancer cases. The introduction of HER2-targeted therapies has transformed the treatment of HER2+ breast cancer and significantly improved survival rates. A major challenge for patients is the development of brain metastases, which can occur in up to 30–50% of patients with breast cancer. Patients with HER2+ breast cancer have a higher risk of developing brain metastases. Immune system cells, specifically T-cells, are one of the few modalities that are capable of crossing the blood brain barrier and may offer an immunologic approach to the prevention of brain metastases in high risk patients. We have been immunizing HER2+ breast cancer patients with HER2 directed vaccines for over 2 decades and sought to determine the impact of HER2-targeted cancer vaccines on the development of brain metastases compared to historical controls. In addition, we will explore the link between the clinical outcomes of patients and the level of immunity they achieved after HER2 specific immunization. Methods: We conducted a retrospective review of 146 patient medical records of advanced stage (III or IV) breast cancer patients, with a HER2+ breast cancer diagnosis confirmed by either IHC 3+ or FISH amplification, who had received a HER2 directed vaccine from one of four clinical trials conducted at the University of Washington, Cancer Vaccine Institute. Patients were followed for the development of brain metastases from the time of initiation of vaccination for at least 5 years. The diagnosis of brain metastases was based on surgical and pathological reports or radiology records and clinical notes from the medical record. IRB approval was obtained prior to initiation of the study. Results: Of the 146 patients with retrospective data, 12 patients had documented brain metastases prior to trial enrollment and were excluded from further evaluation. Of the remaining 134 patients who had no brain metastases at enrollment and subsequently received HER2-targeted vaccines, 21 developed brain metastases, yielding a cumulative incidence (CI) of 15.7%. Stratified by hormone receptor (HR) status, the incidence was 16.9% in HR+/HER2+ patients (n = 13) and 14.5% in HR-/HER2+ patients (n = 8). When compared to a recent historical control cohort of 18,075 real-world patients from the U.S. Flatiron Health database, which reported a 60-month CI of brain metastases of 22.7% in HR+/HER2+ and 33.6% in HR-/HER2+ subgroups, our findings suggest a 26% relative reduction of brain metastases in HR+/HER2+ patients and a 57% reduction in HR-/HER2+ patients. Conclusion: HER2 directed vaccination could have a protective effect on the development of brain metastases in patients with advanced stage HER2+ breast cancer. Phase II trials are planned to prospectively evaluate the vaccine in this setting. Citation Format: Y. Liu, J. Bahia, C. Haghighi, S. Vinayak, J. S. Childs, M. L. Disis. Incidence of the development of brain metastases in patients with advanced stage HER2+ breast cancer who have previously received a HER2 directed cancer vaccine [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 PS5-02-04.