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

Tomás Reinert,Jovana Mandelli,Guilherme Portela Coelho,Facundo Zaffaroni,Edinéia Zimermann,Carlos Henrique Barrios,Marcia Silveira Graudenz,José Bines

doi:10.1155/2019/1947215

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.

Highlights

Estrogen receptor-positive breast cancer is the most common breast cancer subtype
ESR1 mutations (ESR1m) were detected in metastatic tissues from different organs such as pleura (n 3), liver (n 2), lung (n 2), ovary, lymph node, bone, and chest wall. e most frequently detected mutation was the D538G substitution (n 5), followed by mutations in codon 537 (3 Y537N substitutions, 2 Y537C, and 1 Y537S)
ESR1m were detected in 25% (8/32) of the samples, whereas in nonvisceral metastasis, an ESR1m were detected in 6.7% (3/45) of the samples

Summary

Introduction

Endocrine therapy (ET), a targeted treatment to the estrogen receptor (ER) pathway, is the fundamental initial therapeutic approach in all stages of the disease [1]. Clinical resistance associated with progression of disease remains a significant therapeutic challenge [2, 3]. Mutations of the ESR1 gene, which encodes the ER protein, have been increasingly identified as a mechanism of endocrine resistance [4]. E potential clinical implications of ESR1 mutations (ESR1m) remained underappreciated for more than a decade after its discovery since initial studies focused on primary tumors, where the prevalence of ESR1m is very low [5]. ESR1 mutation is a biomarker of worse prognosis and is being evaluated as a predictive biomarker as well as a potential therapeutic target [9]

Methods

Results

Conclusion