ESR1 mutation in Endocrine treatment naive Endometrial Cancer: Prevalence, Characteristics and Prognostic Implications, results from the UTOLA phase II GINECO trial
Abstract
RATIONALE
Aromatase inhibitors (AIs) are used to treat estrogen receptor (ER)-positive low-grade endometrioid EC (LGEC). In breast cancer (BC), ESR1 mutations are rare at diagnosis (<5%) but are frequently acquired in of AI-resistant cases and are considered as one of the major resistance mechanisms to endocrine therapy. This study aimed to assess the prevalence of ESR1 mutations (ESR1m) in homonotherapy-naïve EC samples and correlate with molecular profiles, ER expression and clinical outcomes.
METHODS
147 patients with advanced EC who had responded to first-line chemotherapy were recruited into the UTOLA trial. Archival EC tumor tissues underwent sequencing of 127 genes including ESR1. Only hotspot mutations in the ligand-binding domain were evaluated. ESR1m prevalence was validated in the Genomics England dataset. In UTOLA, tumors were classified as POLE, dMMR, TP53abn or NSMP based on the PROMISE classification.
RESULTS
137/147 patients had sufficient tumor material for sequencing. ESR1m were identified in eight tumors (6%), including Y537S/C/N (N=4), L536H/P (N=2) and E380Q (N=2). A similar prevalence (3.5%) was found among 1311 tumors in the Genomics England dataset. All ESR1m cases were LGEC, ER- and PR-positive and classified as NSMP. Among metastatic NSMP LGEC patients, 22% (8/37) harbored ESR1m. Survival outcomes post-platinum chemotherapy were similar between patients with ESR1m EC and ESR1-wild type (median not reached versus 25.3 months, p=0.114).
CONCLUSION…
Read the paper
Related studies
- Global, regional, and national burden of hepatitis B, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019
- A meta‐analysis of anal cancer incidence by risk group: Toward a unified anal cancer risk scale
- Global fertility in 204 countries and territories, 1950–2021, with forecasts to 2100: a comprehensive demographic analysis for the Global Burden of Disease Study 2021
- Exercise interventions in Alzheimer's disease: A systematic review and meta-analysis of randomized controlled trials
- Prognostic Significance of Carbonic Anhydrase IX Expression in Cancer Patients: A Meta-Analysis
- Glucocorticoid Resistance: Is It a Requisite for Increased Cytokine Production in Depression? A Systematic Review and Meta-Analysis
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.