Pilot study to develop methodologies and acquire data, allowing elucidation of the coordinated control of splicing in oestrogen positive and negative breast cancer tissues.

Although breast cancer treatment has improved over the past few decades and led to increased survival rates and better quality of life, over 44,000 women in the UK are diagnosed with breast cancer each year. Breast cancer remains a significant scientific, clinical and societal challenge. Breast cancers that appear similar by stage

and grade are not identical in terms of outcome for each patient affected. Unfortunately, not enough is known about why treatments don't work for some patients or why breast cancer can return, sometimes many years later. Hence, new markers for early diagnosis, accurate prognosis and prediction of response to treatment are warranted to improve breast cancer care.

The role of oestrogen in breast cancer development, progression and invasion is well known. Oestrogen works as a chemical messenger in the body and implicated in breast cancer by influencing the multiple pathways such as,

1) its role in stimulating breast cell division

2) its work during the critical periods of breast growth and development

3) its effect on other hormones that stimulate breast cell division, and

4) its support of the growth of oestrogen-responsive tumors.

In 2006, the charity Breast Cancer Campaign facilitated a meeting of leading breast cancer experts in the United Kingdom to explore which gaps in research, if filled, would make the most impact on patient benefit.

One of the key areas identified was understanding the functions and contextual interactions of genetic and epigenetic changes taking place during malignant transformation. Since proteomics can bridge the gap between the genetic alterations underlying cancer and cellular physiology, much is expected from proteome analyses for the detection of better protein biomarkers.

This study will be undertaken to study how molecular changes exerted by oestrogen influence the tumor splicing mechanisms as regulators of hormonal signaling in human pathophysiology and cancer.

Initial analyses of this pilot data will use normal and breast cancer tissue (oestrogen positive and negative), while follow-up work can also exploit more advanced machine learning methods.

The commercial interest and translational potential of this area is highlighted by the development of innovative molecular diagnostic products as molecular tests for hormone-resistant cancers, and as predictive biomarkers for responsiveness to treatments (e.g. ExonHit Diagnostics). The project will generate new knowledge, biological tools and datasets and guide future integrated proteomics studies and thus exert a positive impact in the scientific (academic and biotech) community and efforts to uncover the scientific and translational potential of this area.

types, treatment, prognosis and resistance to treatment. In addition it helps to understand the goal of this study is to identify multiple high-throughput proteomic markers and their mechanism of action that regulate gene expression in oestrogen positive and negative tumors. Identification of such proteomic markers in tumour tissue can be used to predict prognosis and therapy outcome in long-term.

Dr Suchita Lal, Academic Clinical Fellow and Specialist trainee in Obstetrics and Gynaecology at UHCW, Coventry