Incidence of ESR1 gene mutations among patients with endometrioid endometrial cancer
Endometrioid endometrial cancer especially low-grade expresses estrogen receptors. A sub-group of patients derives significant benefit from hormonal treatment. The presence of activating ESR1 gene mutations is a common mechanism of resistance to hormonal treatment for patients with breast cancer. We evaluated the incidence of ESR1-activating gene mutations in patients with endometrioid endometrial cancer using the American Association of Cancer Research Genomics Evidence of Neoplasia Information Exchange (v18.0) multi-center data set. A total of 2851 patients with endometrioid endometrial cancer were identified. The overall incidence of ESR1 mutations was 4.0% (n = 113). The incidence of ESR1 mutations was higher among patients with metastatic/recurrent disease than those with primary tumors (7.6% vs 3.4%, p < .001). Patients with ESR1-activating mutations also harbored mTOR/PIK3CA pathway genomic alterations: PTEN (75%), PIK3CA (56%), PIK3R1 (42%), AKT1 (12%). Further research to elucidate the clinical impact of ESR1 gene mutations in endometrial cancer are needed. Clinical trials evaluating novel hormonal agents in this patient population are warranted.