Informing precision medicine by incorporating molecular features in high-risk endometrial cancer

Abstract

The introduction of the molecular classification has significantly enhanced our understanding of the biological mechanisms, clinical behaviour, and optimal therapeutic management of endometrial cancer. The work presented in this thesis address several key areas critical for further improving patient outcomes. These studies have contributed to the enhanced identification of p53abn endometrial cancer and have provided valuable insights into clinically challenging cases, such as those with subclonal abnormal p53 expression and stage I p53abn tumours that appear morphologically low-grade endometrioid. Additionally, ER-status proved to further prognostically refine high-risk NSMP endometrial cancers, offering new perspectives on this heterogenous group of tumours and supporting the potential for personalized treatment approaches in the future. The development of endometrial cancer-specific risk models, incorporating clinicopathological and molecular factors, marks a significant step forward in stratifying patients according to individualized risk profiles, thus improving shared clinical decision-making. Finally, the exploration of HER2 as a druggable target in high-risk, advanced and recurrent endometrial cancer opens new possibilities for targeted therapies. Together, these findings contribute to the growing body of knowledge in endometrial cancer research and pave the way for improved prognostication, enhanced shared clinical decision making, and the development of individualized therapeutic strategies.