A wide range of genetically engineered, patient derived xenograft and cell derived xenograft mouse models have been developed to study ER+ disease, however syngeneic mouse models are lacking. Though there are several breast cancer (BCa) syngeneic cell lines available, most are triple negative in nature. However, there are two published models of ER+ syngeneic BCa cell lines, of which our lab has confirmed only one is a true ER+ line, called the SSM3 cell line (1). To expand on the models available, we have endeavoured to develop a new syngeneic cell line derived from tumours of a K8-PIK3CA/PTEN mouse strain (2). Tumours were mechanically and enzymatically digested to a heterogenous epithelial cell suspension which was sorted on FACS. The entire ER+ (Sca1+) luminal cell subsets (including progenitor and mature cells) were isolated and then plated. Several media types were tested to observe which cell lines would remain luminal cells and maintain ER positivity. Organoid media, rather than SSM33 or colony forming media worked best. Ongoing work is characterising the molecular lineage of these cells and sensitivity to endocrine therapy.