Dataset Information

Association of ESR1 Mutations and Visceral Metastasis in Patients with Estrogen Receptor-Positive Advanced Breast Cancer from Brazil.

ABSTRACT: Mutations in the ESR1 gene (ESR1m) are important mechanisms of resistance to endocrine therapy in estrogen receptor-positive advanced breast cancer and have been recognized as a prognostic and predictive biomarker as well as a potential therapeutic target. However, the prevalence of ESR1m in real-world patients has not been adequately described. Therefore, we sought to evaluate the prevalence of ESR1m in metastatic samples from Brazilian patients with estrogen receptor-positive (ER+) advanced breast cancer previously treated with endocrine therapy. The presence of ESR1m was evaluated in formalin-fixed paraffin-embedded (FFPE) breast cancer tissue using real-time quantitative polymerase chain reaction (RT-qPCR). Mutations in codons 380, 537, and 538 of the ESR1 gene were analyzed. Out of 77 breast cancer samples, 11 (14.3%) showed mutations in the ESR1 gene. ESR1m were detected in a variety of organs, and the D538G substitution was the most common mutation. In visceral metastasis, ESR1m were detected in 25% (8/32) of the samples, whereas in nonvisceral metastasis, ESR1m were detected in 6.7% (3/45) of the samples. The odds of a sample with visceral metastasis having an ESR1 mutation is 4.66 times the odds of a sample of nonvisceral metastasis having an ESR1 mutation (95% CI: 1.13-19.27; p value?=?0.0333). Our study indicates that the prevalence of ESR1m in samples from Brazilian patients with metastatic ER+ breast cancer is similar to that described in patients included in clinical trials. We observed an association of ESR1m with visceral metastasis.

SUBMITTER: Reinert T

PROVIDER: S-EPMC6710809 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association of ESR1 Mutations and Visceral Metastasis in Patients with Estrogen Receptor-Positive Advanced Breast Cancer from Brazil.

Reinert Tomás T Coelho Guilherme Portela GP Mandelli Jovana J Zimermann Edinéia E Zaffaroni Facundo F Bines José J Barrios Carlos Henrique CH Graudenz Marcia Silveira MS

Journal of oncology 20190814

Mutations in the ESR1 gene (ESR1m) are important mechanisms of resistance to endocrine therapy in estrogen receptor-positive advanced breast cancer and have been recognized as a prognostic and predictive biomarker as well as a potential therapeutic target. However, the prevalence of ESR1m in real-world patients has not been adequately described. Therefore, we sought to evaluate the prevalence of ESR1m in metastatic samples from Brazilian patients with estrogen recepto ...[more]

PMID: 31511774

Similar Datasets

Project description:BACKGROUND:ESR1 mutations are frequently detected in ER+ MBC, and have been reported to be associated with endocrine therapy resistance. However, there are little researches to validate whether dynamic monitoring of ESR1 mutations could serve as a predictive plasma biomarker of acquired resistance to endocrine therapy. Therefore, in this study, we performed longitudinal circulating tumor DNA (ctDNA) detection to evaluate the clinical implications of monitoring ESR1 mutations. METHODS:We performed longitudinal dynamic mutation analyses of plasma samples from 45 patients with metastatic breast cancer (MBC) and sequencing paired biopsy tissues, using a targeted NGS panel of 425 genes. These patients were treated at the Second Affiliated Hospital of Dalian Medical University between January 2017 and February 2019 with written informed consent. RESULTS:Mutations profiles were highly concordant between plasma and paired tissue samples from 45 MBC patients (r = 0.96, P < 0.0001). ESR1 mutations were enriched in ER+ MBC patients after AI therapy (17.8%, 8/45). The median time from AI endocrine therapies to the initial detection of ESR1 mutation was 39 months (95% CI 21.32-57.57). Some hotspot mutations (Y537S (n = 5), Y537N (n = 1), D538G (n = 2), E380Q (n = 2)) and several rare mutations (L345SfsX7, 24fs, G344delinsGC) were identified in our cohort. In addition, we observed that two patients obtained multiple ESR1 mutations over the course of treatment (Y537N/Y537S/D538G, L345SfsX7/24fs/E380Q). Through dynamically monitoring ESR1 mutations by ctDNA, we demonstrated that the change of allele frequency of ESR1 mutations was an important biomarker, which could predict endocrine resistance of ER+ MBC in our study. We also observed that the combination of everolimus in four cases with acquired ESR1 mutations showed longer PFS than other therapies without everolimus. CONCLUSION:The dynamic monitoring of ESR1 mutations by ctDNA is a promising tool to predict endocrine therapy resistance in ER+ MBC patients.

Dataset Information

Association of ESR1 Mutations and Visceral Metastasis in Patients with Estrogen Receptor-Positive Advanced Breast Cancer from Brazil.

Publications

Association of <i>ESR1</i> Mutations and Visceral Metastasis in Patients with Estrogen Receptor-Positive Advanced Breast Cancer from Brazil.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets