<p>Prevalence of ESR1 Mutation in Chinese ER-Positive Breast Cancer</p>

Abstract

Background: ESR1 mutation and its possible relation to endocrine therapy resistance in ERpositive breast cancers have been studied with respect to genetic sequencing data from Western patients but rarely from Chinese patients. This study aimed to investigate the prevalence of ESR1 mutation in Chinese primary and metastatic ER-positive breast cancer. Methods: Tumor samples from 297 primary breast cancer (PBC) patients and blood samples from 43 metastatic breast cancer (MBC) patients were obtained to perform whole exon sequencing of the ESR1 gene through next-generation sequencing (NGS). Clinicopathological features of MBC patients were listed and grouped to explore potential factors in ESR1 mutations. Results: A total of 15 ESR1 variations, including 11 point mutations, 1 in-frame deletion mutation, 1 synonymous mutation, and 2 amplifications were identified in 13 patients. The ESR1 mutation rate was 1% (3/297) in PBC patients and 18.6% (8/43) in MBC patients. All ESR1 point mutations occurred in the estrogen receptor ligand-binding domain. Six (54.5%) of the 11 point mutations were hotspot mutations. Among all MBC patients, the ESR1 mutation rate in those who had a treatment history using aromatase inhibitors (AI) was significantly higher than those who did not (25.8% versus 0%, P=0.015). Moreover, the ESR1 mutation rate in those who received AI treatment over a period of 12 months was significantly higher than in those whose treatment lasted less than 12 months [36.3% versus 0%, P<0.001]. Conclusion: ESR1 mutations were more frequently observed in the circulating cell-free DNA of MBC patients than in PBC patients among the Chinese cohort, and higher among those pretreated with AI, suggesting that such mutations may undergo selection during AI treatment.

Characterization of Frequently Mutated Cancer Genes and Tumor Mutation Burden in Chinese Breast Cancer

“…Since these mutations are missense mutations that can only be detected by DNA-based analysis using NGS or digital PCR, they may be missed by the conventional methods of HER2 assays. The ESR1 mutation status of breast cancer is associated with resistance to endocrine therapy (21). In our cohort, 2.7% (16/589) of the patients have ESR1 mutations, with 69% (11/16) of the patients harboring ESR1 mutation had stage III breast cancer.…”

Detection of ESR1 Mutations Based on Liquid Biopsy in Estrogen Receptor-Positive Metastatic Breast Cancer: Clinical Impacts and Prospects

“…Importantly, numerous studies have identified the prognostic role of ESR1 mutations in MBC patients who received AIs 17, 27, 39, 43, 44). The rate of ESR1 mutations in ER+ MBC patients who progressed on AIs treatment was significantly higher than that of AIs-naïve patients (25.8% vs. 0%; P = 0.015) ( 43 ). Li et al.…”

“…Large-scale clinical trials of recent years detecting ESR1 mutations in metastatic breast cancer (MBC).AIs 17,27,39,43,44). The rate of ESR1 mutations in ER+ MBC patients who progressed on AIs treatment was significantly higher than that of AIs-naïve patients (25.8% vs. 0%; P = 0.015)(43).…”

“…Large-scale clinical trials of recent years detecting ESR1 mutations in metastatic breast cancer (MBC).AIs 17,27,39,43,44). The rate of ESR1 mutations in ER+ MBC patients who progressed on AIs treatment was significantly higher than that of AIs-naïve patients (25.8% vs. 0%; P = 0.015)(43). Li et al demonstrated that the change of MAF in circulating ESR1 was an important biomarker in ER+ MBC, which could predict the resistance to AIs(44).…”

Estrogen Receptor Bio-Activities Determine Clinical Endocrine Treatment Options in Estrogen Receptor-Positive Breast Cancer

“…The rate of ESR1 mutations was significantly higher in ER+ MBC patients who progressed to AI resistance than in those who did not (25.8% vs 0%; P = .015). 138 Interestingly, a very low rate of ESR1 mutations was in patients with MBC treated with AIs in adjuvant therapy, but not in metastatic therapy. 139 This conclusion was also confirmed in a French trial, PADA-1, 140 in which only 3.2% (26 of 811) of patients diagnosed with stage IV HR + BC had ESR1 mutations detected in any pretreatment ctDNA.…”