The Molecular Landscape of Endometrial Cancer

This seminar will outline the molecular changes common to endometrial cancers. It will review the application of molecular and other changes to understand the four recognised subgroups of endometrial cancers and what this may mean prognostically and for treatment decisions. Use of molecular sequencing remains uncommonplace and unfunded in uterine cancer, the derived use of histopathology features together with minimal molecular screening for POLE hypermutations have been used to derive the ProMisE model – is this applicable to an Australian population and how might this be used to triage patients for treatment decisions? With the first funded change to treatments in more than 40 years announced recently for endometrial cancers, the use of immune checkpoint inhibitors will result in a dramatic change to first and subsequent lines of therapy in the advanced cancer setting with ongoing research in the adjuvant and neoadjuvant setting. The importance of molecular alterations and how this might impact the tumour microenvironment to influence immunotherapy  is therefore of increasing importance and will be reviewed. Finally, tumour molecular alterations may reflect germline origins- when to consider referral for hereditary assessment may influence both patient management together with an improvement in cancer prevention for both the patient and their family.