70% breast cancer patients are ER positive and in such tumours endocrine therapy is an important treatment which improves overall survival as shown by the Early Breast Cancer Trialists' Collaborative Group (EBCTCG Lancet, 2011, 378:771-784).. However, endocrine resistance both de novo and acquired remain major issues and limit their use. The aim of this project is to explore the oestrogen receptor (ER) cistrome prior to and following 2-3 weeks of endocrine therapy with the aromatase inhibitor letrozole. The letrozole will be administered in the 2-3 week period between diagnosis and surgery, such studies are known as window studies and are well established in breast cancer. Using ChIP-Seq ER binding events will be analysed pre-and post- treatment, and Ki67 (marker of tumour proliferation) utilised to stratify patients between responders and non-responders to treatment. It is postulated that ER-binding events will differ in the responder vs non-responder group.In-vitro ChIP-seq work will also be performed in endocrine resistant and responsive breast cancer cell-lines to further understand the molecular mechanisms involved in endocrine responsive and resistant disease. It is hoped that this may established a ChIP-Seq signature for resistance to endocrine therapy and identify possible novel targets which could lead ultimately to new treatments to prevent or treat endocrine resistance.