Incidence of ESR1 gene mutations among patients with endometrioid endometrial cancer

Area of Science:

• Oncology
• Genomics
• Molecular Biology

Background:

• Endometrioid endometrial cancer often expresses estrogen receptors, making hormonal therapy a viable treatment for some patients.
• Activating ESR1 gene mutations are a known cause of resistance to hormonal therapy in breast cancer.
• The role of ESR1 mutations in endometrial cancer, particularly regarding treatment resistance, requires further investigation.

Purpose of the Study:

• To determine the incidence of ESR1-activating gene mutations in endometrioid endometrial cancer.
• To explore the association between ESR1 mutations and disease stage (primary vs. metastatic/recurrent).
• To investigate co-occurring genomic alterations in pathways like mTOR/PIK3CA among patients with ESR1 mutations.

Main Methods:

• Utilized the American Association of Cancer Research Genomics Evidence of Neoplasia Information Exchange (v18.0) multi-center data set.
• Analyzed genomic data from 2851 patients diagnosed with endometrioid endometrial cancer.
• Assessed the frequency of ESR1 mutations and correlated them with clinical data and other genomic alterations.

Main Results:

• The overall incidence of ESR1 mutations in endometrioid endometrial cancer was 4.0% (113 out of 2851 patients).
• ESR1 mutation incidence was significantly higher in patients with metastatic or recurrent disease (7.6%) compared to those with primary tumors (3.4%; p < .001).
• Patients with ESR1-activating mutations frequently exhibited co-occurring genomic alterations in the mTOR/PIK3CA pathway, including PTEN (75%), PIK3CA (56%), PIK3R1 (42%), and AKT1 (12%).

Conclusions:

• ESR1-activating mutations are present in a notable subset of endometrioid endometrial cancer patients, particularly those with advanced disease.
• The co-occurrence of ESR1 mutations with mTOR/PIK3CA pathway alterations suggests complex molecular mechanisms in endometrial cancer.
• Further research and clinical trials are warranted to understand the clinical impact of ESR1 mutations and to evaluate novel hormonal agents in endometrial cancer.