Why do we continue to have an incomplete understanding of estrogen receptor(s) actions in cancer systems?

The topic proposed asks why we have an incomplete understanding of estrogen receptor (ER) action in cancer. We agree that the role of ER in some cancers is poorly understood, but the role of ER in luminal breast cancer (which represents the biggest subtype of the most common cancer in women) is very well characterised. Although technologies evolve and allow us to learn more about the intricacies of the genome and the multitude of ways breast cancer can adapt to bypass treatments, our understanding of how ER regulates gene expression is extraordinary. We would posit that the key events in ER-mediated cell cycle progression are already known and although new information adds granular information to our paradigms of ER action, we need to better characterise what has been discovered already.