Hormone receptor expression remains prognostically relevant in endometrial cancer

Endometrial cancer has historically, been classified based on hormone dependent (Type 1) and independent (type 2) pathways. Type 1 represented 80% of all new diagnosis with generally low-grade tumors associated with obesity and good prognosis, whereas type 2 represents high-grade tumors with mainly low estrogen (ER) and progesterone (PR) expression and poor outcome.

Currently used cutoff for ER/PR expression within endometrial cancer is adopted from breast cancer studies, and most frequently considered >10% expression positive. We previously explored different cutoff values for ER/PR expression and showed the subgroups 0–10 % with unfavorable outcome, 20–80 % with intermediate outcome and 90–100 % with favorable outcome.

Since the introduction of the four molecular subgroups defined by one with worst outcome (p53mut), two with intermediate outcome (MMRd, NSMP) and one with favorable outcome (POLEmut), the relevance of hormone receptor expression has gained less interest.

Stephanie Vrede investigated this relevance within the molecular subgroups in a large set of patients with endometrial cancer within the European Network of Individual Treatment in Endometrial Cancer (ENITEC) consortium in collaboration with the group of Jessica McAlpine (Vancouver, BC). The research group Translational research gynecological oncology, led by Hanny Pijnenborg , Dept Obstetrics & Gynecology, published the results in Gynecologic Oncology on November 7, 2024.

We demonstrated in the current paper including 739 patients that among all molecular subgroups, patients with hormone expression 90–100 % expression revealed the best survival. Across all molecular subgroups, PR 0–10 % expression and one of the most aggressive molecular subgroup remained independently prognostic for reduced survival. Whereas PR 90–100 % expression and one of the most favorable molecular subgroup remained independently prognostic for improved survival.

We demonstrated that ER/PR expression remains prognostically relevant even within molecular subgroups, and that a three-tiered cutoff refines prognostication. These data support incorporating routine evaluation of ER/PR expression in clinical practice.  Our next step is to evaluated the relation of hormone expression within the genetic pathways of the intermediate molecular subgroup ‘no-specific molecular profile (NSMP)’.

In this genomic era the secret of surviving is knowing what to keep and to combine.

About the publication

Vrede SW, Van Weelden WJ, Bulten J, Gilks CB, Teerenstra S, Huvila J, Matias-Guiu X, Gil-Moreno A, Asberger J, Sweegers S, van der Putten LJM, Küsters-Vandevelde HVN, Reijnen C, Colas E, Hausnerová J, Weinberger V, Snijders MPLM, Vinklerova P, Ravaggi A, Odicino F, Bignotti E, McAlpine JN, Kruitwagen R, Pijnenborg JMA. Hormonal biomarkers remain prognostically relevant within the molecular subgroups in endometrial cancer. Gynecol Oncol. 2024 Nov 7;192:15-23. doi: 10.1016/j.ygyno.2024.10.028.