Development of immunocompetent models for primary and metastatic <scp>ER</scp> + breast cancer

BACKGROUND: The development of effective therapeutic strategies for late-stage estrogen receptor-positive breast cancer (ER+) is limited by the scarcity of biologically relevant models. More recently, immunotherapies emerged as promising candidates for breast cancer treatment, however, the absence of immunocompetent models of ER+ breast cancer metastasis continues to hinder the assessment of these theraputic interventions. METHODS: To address this, we utilized the 129S6/SvEv mouse strain and syngeneic SSM3 cells in the assessment and development of ER+ metastasis models. As part of this study, the mammary intraductal (MIND) primary tumor model was established in the same background. In addition, a novel luciferase system was evaluated for potential use in metastasis tracking. RESULTS: Luciferase-expressing SSM3 cells enabled longitudinal in vivo imaging to track tumor growth. Histological analysis confirmed metastatic spread and tumor origin. Antares2, a novel luciferase reporter, showed high in vitro sensitivity but reduced in vivo performance. The study showed that systemic delivery of SSM3 cells with oestradiol supplementation can support metastatic tumor establishment and that MIND injections led to reliable, invasive tumor growth. CONCLUSIONS: These findings highlight the potential and limitations of the 129S6/SvEv model as a syngeneic, immunocompetent system for studying ER+ breast cancer metastasis. Reporter expression may affect immunogenicity or cell fitness. Further refinement of these models will enable investigation of immune-modulatory therapies in ER+ metastatic breast cancer.