番茄社区

Endometrial cancer is currently the sixth most common malignancy in women worldwide, accounting for approximately 97,000 deaths per year and with rapidly increasing incidence. The disease can be characterized based on molecular signatures into four prognostically distinct subgroups:

• Ultramutated tumors characterized by POLE hotspot mutations with excellent prognosis

• Hypermutated tumors characterized by mismatch repair deficiency resulting in microsatellite instability with intermediate prognosis

• Tumors with no specific molecular profile (NSMP) or copy-number low (p53 wild-type) with intermediate prognosis

• Copy-number high tumors, characterized by TP53 mutations (p53abn) and poor prognosis

This molecular classification only partly overlaps with the classical histologic classification in which endometrial cancer was subdivided into estrogen-related type 1 tumors (endometrioid endometrial cancer, generally with good prognosis) and unrelated to estrogen type 2 tumors (nonendometrioid endometrial cancer with poor outcome).

All four molecular subgroups are present across type 1 and 2 tumors. However, type 1 tumors are mainly represented by the NSMP group (90% grade 1-2; 85% International Federation of Gynecology and Obstetrics staging system [FIGO] I), whereas type 2 tumors by the TP53-mutant group (91% grade 3; 45% FIGO I).

Hormonal drugs represent valuable therapeutic agents in the treatment of endometrial cancer, both in the early-stage and as palliative treatment. Application of hormonal therapy in patients with endometrial cancer should be based on ER/PR expression. Preliminary data support the integration of hormone signaling biomarkers that better reflect hormone signaling activation to facilitate clinical use of hormonal therapy.

Results from active trials are awaited to better understand how and to whom hormonal drugs should be indicated. Finally, yet importantly, hormonal therapy is cost effective and can be administered orally, allowing application in regions with impaired accessibility to specialized infrastructures and low resources.

Read an interview about the "Comments and Controversies" article here and expert commentary about it here.