In breast cancer, the most prevalent female cancer, mortality occurs not because of the primary tumour burden but due to metastatic disease. Harnessing the immune system to elicit regression of established tumours has proved successful in many cancers, however, controlling metastatic disease remains a greater challenge. Regulatory T cells (Tregs) play a dominant role in suppressing effective T cell responses within the tumour microenvironment. Studies to date, have demonstrated in preclinical models of solid tumours that ablation of Tregs, using transgenic mouse models, controls primary tumour growth but does not control metastatic disease. We utilised the 4T1 model of mammary carcinoma, that recapitulates many of the hallmarks of human disease, such as metastatic potential with increased tumour burden and an accumulation of myeloid derived suppressor cells (MDSCs) within the periphery, to examine alternative strategies to suppress Treg function within the tumour. A small molecule inhibitor of the PI3K pathway (PI-3065), that specifically targets the p110δ subunit expressed by leukocytes, with a high activity on Tregs, was administered to tumour-bearing mice. We observed that PI-3065- treated mice had reduced tumour burden, with approximately 15-20% of hosts eradicating the primary tumour. PI-3065 treatment prevented peripheral MDSC expansion, resulting in a significant reduction in lung metastases, with a direct association between primary tumour burden and metastatic load evident. Interestingly, PI-3065 treatment was also associated with altered blood vessel formation within the tumour, which may aid immune cell infiltration. Depletion of CD8+ T cells abrogated the control of primary tumour growth elicited by PI-3065 treatment, demonstrating that the development of an anti-tumour T cell response is critical in controlling both metastatic disease and primary tumour burden in breast cancer.