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

Abstract

Mutations in the <i>ESR1</i> gene (<i>ESR1m</i>) 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 <i>ESR1m</i> in real-world patients has not been adequately described. Therefore, we sought to evaluate the prevalence of <i>ESR1m</i> in metastatic samples from Brazilian patients with estrogen receptor-positive (ER+) advanced breast cancer previously treated with endocrine therapy. The presence of <i>ESR1m</i> 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 <i>ESR1</i> gene were analyzed. Out of 77 breast cancer samples, 11 (14.3%) showed mutations in the <i>ESR1</i> gene. <i>ESR1m</i> were detected in a variety of organs, and the D538G substitution was the most common mutation. In visceral metastasis, <i>ESR1m</i> were detected in 25% (8/32) of the samples, whereas in nonvisceral metastasis, <i>ESR1m</i> were detected in 6.7% (3/45) of the samples. The odds of a sample with visceral metastasis having an <i>ESR1</i> mutation is 4.66 times the odds of a sample of nonvisceral metastasis having an <i>ESR1</i> mutation (95% CI: 1.13-19.27; <i>p</i> value = 0.0333). Our study indicates that the prevalence of <i>ESR1m</i> 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 <i>ESR1m</i> with visceral metastasis.