The aim of the Breakthrough Breast Cancer Research Unit, at the University of Edinburgh, is to analyse genetic, epigenetic and gene expression change in patients with breast cancer treated by hormone therapies, to improve patient care by better targeting of endocrine and novel therapies.
Background
Not all patients treated with hormone therapy benefit although all suffer side effects from treatment. In the three quarters of patients with breast cancers have receptors for oestrogen, at most two thirds respond. Those that do respond eventually develop resistance.
The Edinburgh Breast Unit has established a series of clinical models. In the preoperative model, patients with early breast cancer are treated with different agents for between 10 to 14 days while awaiting definitive surgery. In the neoadjuvant model, patients with larger tumours are treated with systemic or neoadjuvant therapy for 3 months or longer. The value of these longer durations of treatment is that early changes within the tumour can be related to longer term response. By obtaining tissue before, during and after treatment, it is possible within these cancers to identify signatures for response and different patterns of resistance.
Our aim
The aim of the Breakthrough Research Unit, Edinburgh is to investigate how cancers respond to endocrine therapy and study mechanisms involved in both de novo and acquired resistance and develop potential new targets for treatment. By bringing together a team of highly regarded clinicians and scientists, drawn from the Edinburgh Breast Unit, the Department of Pathology, the Human Genetics Unit and the Edinburgh Cancer Research Centre, a new and exciting collaborative group has been forged which will allow expansion of breast cancer research in Edinburgh.
Our research
Many previous studies have relied on single methods of analysis such as transcriptomics or molecular pathology alone. Our studies will provide an in depth analysis using clinical material derived from a series of patients treated with endocrine novel agents. As well as studying gene expression in breast cancer at both the transcriptome and gene expression level, we will also look at the epigenetic changes and define the underlining mutational status as assessed by SNP chip analysis. Investigation of epigenetic changes will also include changes in DNA methylation, histone modifications, and clinical and scientific research proteins that interpret these epigenetic markers by binding to the modified chromatin to effect changes in gene transcription. This combined approach, bringing together under the Breakthrough umbrella, the Edinburgh Breast Unit’s clinical and scientific research combined with local expertise in informatics and computational systems biology, should provide a comprehensive insight into the mechanisms of hormone resistance and sensitivity.
