Social Card Image three Social Card Image two Social Card Image seven Social Card Image six Social Card Image five Social Card Image four Social Card Image one


Prevalence of ESR1 Mutations in Low-Grade NSMP EC & AIs Resistance

June, 06, 2024 | Gynecologic Cancer, Uterine Cancer


  • The UTOLA phase 2 trial aimed to identify the correlation between ESR1 mutations, molecular profiles, and ER expression in pts with untreated EC.
  • The ESR1 mutations in LBD were found to be prevalent in relapsed/metastatic low-grade NSMP EC.

The trial determined the prevalence of ESR1 mutations (ESR1m) in samples obtained from a cohort of patients (pts) with previously untreated endometrial cancer (EC) samples and attempted to establish a correlation between the presence of mutations with the molecular profiles, expression of estrogen receptor (ER), and clinical outcomes.

Aromatase inhibitors (AIs) are considered a therapeutic alternative for ER+ EC, particularly in cases of low-grade EC. ESR1 somatic mutations can lead to constitutive ligand-independent activation of ER and have been associated with resistance to AIs in breast cancer (BC). While these mutations are rare at the time of BC diagnosis (<1%), they occur in up to 36% of cases that develop resistance to AIs.

Felix Blanc-Durand and the team designed this trial to correlate the prevalence of ESR1 mutations (ESR1m) with the molecular profiles, ER expression, and clinical outcomes.

Felix Blanc-Durand and the team designed this trial to correlate the prevalence of ESR1 mutations (ESR1m) with the molecular profiles, ER expression, and clinical outcomes.

About 147 pts with relapsed/metastatic EC who had achieved disease control after first-line platinum chemotherapy (chemo) were enrolled in the trial. Archival EC formalin-fixed, paraffin-embedded (FFPE) tumor tissues were analyzed using a comprehensive sequencing panel covering 127 genes, including ESR1. Only previously reported hotspot mutations in the ligand-binding domain (LBD) were considered for the analysis. As per the PROMISE classification tumors were categorized as POLE, MMRd, TP53mut, or NSM.

Results revealed that of 147 pts, 137 (93%) had sufficient tumor material for sequencing. Pathogenic ESR1 mutations were identified in eight tumors (6%), including specific mutations Y537S/C/N (n=4), L536H/P (n=2), and E380Q (n=2).

All cases with ESR1 mutations exhibited low-grade endometrioid histology, were ER-positive, and were classified as NSMP. Among the 43 pts with metastatic endometrioid NSMP EC, 19% (8/43) had ESR1 mutations in archival treatment-naive tumor tissue.

In terms of outcomes, overall survival was similar between pts with ESR1-mutant EC and those with ESR1-wild type NSMP EC, with median survival not reached in the ESR1-mutant group compared to 25.3 months in the ESR1-wild type group (P=0.114).

The study concluded that ESR1 mutations in the LBD were commonly seen in relapsed/metastatic low-grade endometrioid NSMP EC; detected in nearly 20% of treatment-naive cases. These mutations suggest AIs, pinpointing the impact of ESR1 status when selecting hormonal therapies and in AI trials.

The trial was sponsored by ARCAGY/ GINECO GROUP.

Clinical Trial:

Durand F B, Nikolaev S, Leman R, et al. (2024). “ESR1 mutation in untreated endometrial cancer: Prevalence, characteristics and prognostic implications from the UTOLA trial.” Presented at ESMO-GC 2024, (Abstract 41MO)

For Additional News from OncWeekly – Your Front Row Seat To The Future of Cancer Care –




Sign up for our emails

Trusted insights straight to your inbox and get the latest updates from OncWeekly

Privacy Policy