AUTHOR=Reinert Tomás , do Rego Fernanda Orpinelli , Silva Matheus Costa e , Rodrigues Amanda Muniz , Koyama Fernanda Christtanini , Gonçalves Aline Coelho , Pauletto Maiane Maria , de Carvalho Oliveira Leandro Jonata , de Resende Cristiano Augusto Andrade , Landeiro Luciana Castro Garcia , Barrios Carlos Henrique , Mano Max Senna , Dienstmann Rodrigo 

TITLE=The somatic mutation profile of estrogen receptor-positive HER2-negative metastatic breast cancer in Brazilian patients

JOURNAL=Frontiers in Oncology

VOLUME=14

YEAR=2024

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1372947

DOI=10.3389/fonc.2024.1372947

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p>Breast cancer is the leading cause of cancer death among women worldwide. Studies about the genomic landscape of metastatic breast cancer (MBC) have predominantly originated from developed nations. There are still limited data on the molecular epidemiology of MBC in low- and middle-income countries. This study aims to evaluate the prevalence of mutations in the PI3K-AKT pathway and other actionable drivers in estrogen receptor (ER)+/HER2- MBC among Brazilian patients treated at a large institution representative of the nation’s demographic diversity.</p></sec><sec><title>Methods</title><p>We conducted a retrospective observational study using laboratory data (OC Precision Medicine). Our study included tumor samples from patients with ER+/HER2- MBC who underwent routine tumor testing from 2020 to 2023 and originated from several Brazilian centers within the Oncoclinicas network. Two distinct next-generation sequencing (NGS) assays were used: GS Focus (23 genes, covering <italic>PIK3CA</italic>, <italic>AKT1</italic>, <italic>ESR1</italic>, <italic>ERBB2</italic>, <italic>BRCA1</italic>, <italic>BRCA2</italic>, <italic>PALB2</italic>, <italic>TP53</italic>, but not <italic>PTEN</italic>) or GS 180 (180 genes, including PTEN, tumor mutation burden [TMB] and microsatellite instability [MSI]).</p></sec><sec><title>Results</title><p>Evaluation of tumor samples from 328 patients was undertaken, mostly (75.6%) with GS Focus. Of these, 69% were primary tumors, while 31% were metastatic lesions. The prevalence of mutations in the PI3K-AKT pathway was 39.3% (95% confidence interval, 33% to 43%), distributed as 37.5% in <italic>PIK3CA</italic> and 1.8% in <italic>AKT1</italic>. Stratification by age revealed a higher incidence of mutations in this pathway among patients over 50 (44.5% vs 29.1%, p=0.01). Among the <italic>PIK3CA</italic> mutations, 78% were canonical (included in the alpelisib companion diagnostic non-NGS test), while the remaining 22% were characterized as non-canonical mutations (identifiable only by NGS test). <italic>ESR1</italic> mutations were detected in 6.1%, exhibiting a higher frequency in metastatic samples (15.1% vs 1.3%, p=0.003). Additionally, mutations in <italic>BRCA1, BRCA2</italic>, or <italic>PALB2</italic> were identified in 3.9% of cases, while mutations in <italic>ERBB2</italic> were found in 2.1%. No <italic>PTEN</italic> mutations were detected, nor were TMB high or MSI cases.</p></sec><sec><title>Conclusion</title><p>We describe the genomic landscape of Brazilian patients with ER+/HER2- MBC, in which the somatic mutation profile is comparable to what is described in the literature globally. These data are important for developing precision medicine strategies in this scenario, as well as for health systems management and research initiatives.</p></sec>