Estrogen receptor alpha in breast cancer – one gene, multiple proteins, many functions

Estrogen receptor alpha (ER) is the most important breast cancer biomarker in clinical practice; it provides prognostic information, guides the choice of treatment and is also the target of a number of cancer therapies. Although there are a few known alternative protein isoforms of the ER, these are currently not taken into consideration in clinical management of breast cancer. We have analysed RNA sequencing data from 3500 breast tumours and identified a large number of new ER isoforms with considerable variation among patients. These isoforms are created by a combination of alternative promoters and alternative splicing. We wish to clarify what role the different isoforms have in tumour biology, treatment response and resistance development. In the future, perhaps measuring the expression of individual isoforms will help identify the best treatment strategy, especially in patients with recurrence or disease progression.