HER2-positive central nervous system (CNS) surveillance: A study of the feasibility of randomizing women and men with HER2-positive metastatic breast cancer to CNS surveillance versus no surveillance.

Abstract

TPS1146 Background: Breast cancer (BC) is the second most common primary tumour to metastasise to the brain (Aragon-Ching, 2017). Clinical data have demonstrated that BC brain metastases (BCBM) are an increasing clinical problem (Akshara, 2024). Improved systemic treatment of extracranial disease has prolonged survival (DESTINY-Breast9, 2025); coupled with more CNS imaging, this likely contributes to rising BCBM incidence (Frisk, 2012; Pedrosa, 2018). HER2+ BC has a predilection for the CNS (Sun, 2022), and real-world data from the ESMÉ programme report BCBM incidence in metastatic BC (MBC) (Darlix, 2019). Cumulative incidence at 12 months after MBC diagnosis in a cohort of 16,703 MBC pts was 16.8% and 32.4% for HER2+ /HR+ and HER2+ /HR- respectively; at 24 months, 29.2% and 49.0%, respectively. Given the high risk of CNS disease in HER2+ MBC, associated morbidity/mortality (Riecke, 2023) and the evidence that there may be a survival and quality of life advantage for early asymptomatic detection (Hurvitz, 2019; Laakmann, 2020), surveillance strategies for early detection need evaluation. Methods: This is a multi-centre, randomised study in pts with HER2+ MBC without prior CNS disease. The study is testing the feasibility of randomising pts to CNS screening vs none. The study is recruiting male/female pts, aged ≥16 years with HER2+ BC with visceral metastases who are currently on HER2 directed therapies. It excludes pts with a history/clinical symptoms of CNS disease, unable to undergo MRI, or with bone only MBC. Pts following a baseline MRI brain, to exclude occult disease, are randomised 1:1 to 6 monthly MRI brain with contrast for a year or no CNS imaging. Primary endpoint: feasibility of randomising HER2+ MBC pts with no CNS disease to surveillance vs no surveillance. Secondary endpoints: proportion of pts with occult CNS disease at baseline, proportion developing occult CNS disease during surveillance and proportion developing symptomatic CNS disease during the study. The management of detected CNS disease on study will be documented. Further qualitative research through a series of interviews/focus group discussions will explore reasons why pts either agree/refuse randomization, to identify challenges with study implementation and delivery. Statistics: A maximum of 193 pts are to be approached; with 69 pts agreeing to be consented to the study for a larger study to be deemed feasible (based on alpha=5% and power 90%). Recruitment will halt at 69 consented/193 approached, whichever is reached first. REC/IRAS project ID: 341272.