Invasive lobular breast cancer (ILC) represents 10-15% of all newly diagnosed breast cancers and has a distinct pattern of metastatic spread, with a greater propensity to develop ovarian, GI and leptomeningeal metastasis where the tumour spread is typically over the serosal surfaces rather than infiltrating into the parenchyma. In addition, lobular breast cancers have poor long-term outcome indicative of a latent metastatic phenotype. The genetics of ILC have been well studied, however the biology of ILC is poorly understood due to the paucity of clinically relevant models. To identify therapeutic vulnerabilities associated with ILC, we will develop improved in vitro, ex vivo and in vivo models and interrogate the biology of ILC metastatic colonisation – focusing on the pattern of metastatic spread in the peritoneum and leptomeninges. In parallel we will collect liquid biopsies (ascitic fluid and cerebrospinal fluid) from ILC patients for ultra-low-pass and whole exome sequencing to identify potential drivers of metastatic spread, determine the clonal evolution of ILC metastasis and for the development of diagnostic and disease monitoring biomarkers.