Reprogrammed oestrogen binding linked to more aggressive breast cancer

Researchers have discovered how receptors for the female sex hormone oestrogen attach to a different part of the DNA in breast cancer patients who are more likely to relapse. Understanding the genetic differences that determine who will or won't respond to a given treatment is a vital step in being able to choose the right drugs for individual patients." - —Carlos Caldas, Professor of Cancer Medicine at the Department of Oncology at the University of Cambridge and the Cancer Research UK Cambridge Research Institute Scientists based at the Cancer Research UK Cambridge Research Institute have discovered how receptors for the female sex hormone oestrogen attach to a different part of the DNA in breast cancer patients who are more likely to relapse, according to a study published in Nature . Crucially, they also found that within these more aggressive breast cancers, the oestrogen receptor (ER) was being 'redirected' to a different part of the genome by a protein called FOXA1. So drugs that specifically block FOXA1 could help treat patients who do not respond to conventional hormone treatments, such as tamoxifen. The researchers used state of the art technology, called ChIP sequencing, to analyse ER-genome interactions in frozen breast tumour samples and create a map of all of the sites in the human genome where ER attaches itself to the DNA and switches on particular genes. This map was used to compare where in the genome ER attached in tumours from people that responded well to treatment, versus those that went on to relapse or were resistant to treatment from the start.