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Abstract：
UNASSIGNED: 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.
UNASSIGNED: 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 PIK3CA, AKT1, ESR1, ERBB2, BRCA1, BRCA2, PALB2, TP53, but not PTEN) or GS 180 (180 genes, including PTEN, tumor mutation burden [TMB] and microsatellite instability [MSI]).
UNASSIGNED: 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 PIK3CA and 1.8% in AKT1. 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 PIK3CA 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). ESR1 mutations were detected in 6.1%, exhibiting a higher frequency in metastatic samples (15.1% vs 1.3%, p=0.003). Additionally, mutations in BRCA1, BRCA2, or PALB2 were identified in 3.9% of cases, while mutations in ERBB2 were found in 2.1%. No PTEN mutations were detected, nor were TMB high or MSI cases.
UNASSIGNED: 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.
UNASSIGNED: 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 PIK3CA, AKT1, ESR1, ERBB2, BRCA1, BRCA2, PALB2, TP53, but not PTEN) or GS 180 (180 genes, including PTEN, tumor mutation burden [TMB] and microsatellite instability [MSI]).
UNASSIGNED: 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 PIK3CA and 1.8% in AKT1. 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 PIK3CA 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). ESR1 mutations were detected in 6.1%, exhibiting a higher frequency in metastatic samples (15.1% vs 1.3%, p=0.003). Additionally, mutations in BRCA1, BRCA2, or PALB2 were identified in 3.9% of cases, while mutations in ERBB2 were found in 2.1%. No PTEN mutations were detected, nor were TMB high or MSI cases.
UNASSIGNED: 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.
摘要：
乳腺癌是全球女性癌症死亡的主要原因。关于转移性乳腺癌（MBC）基因组景观的研究主要起源于发达国家。在低收入和中等收入国家，关于MBC分子流行病学的数据仍然有限。本研究旨在评估PI3K-AKT通路突变和雌激素受体（ER）+/HER2-MBC其他可行驱动因素在巴西患者中的患病率，该患者在代表国家人口多样性的大型机构接受治疗。
■我们使用实验室数据进行了回顾性观察研究（OC精准医学）。我们的研究包括ER+/HER2-MBC患者的肿瘤样本，这些患者从2020年到2023年接受了常规肿瘤检测，并且起源于Oncoclinicas网络内的几个巴西中心。使用了两种不同的下一代测序（NGS）测定：GSFocus（23个基因，涵盖PIK3CA，AKT1，ESR1，ERBB2，BRCA1，BRCA2，PALB2，TP53，但不是PTEN）或GS180（180个基因，包括PTEN,肿瘤突变负荷[TMB]和微卫星不稳定性[MSI])。
■对328名患者的肿瘤样本进行评估，大部分（75.6%）与GSFocus。其中,69%为原发肿瘤,而31%为转移性病灶。PI3K-AKT通路突变的患病率为39.3%(95%置信区间,33%至43%），在PIK3CA中分布为37.5%，在AKT1中分布为1.8%。按年龄分层显示，在50岁以上的患者中，该通路突变的发生率更高（44.5%vs29.1%，p=0.01)。在PIK3CA突变中，78%是规范的(包括在alpelisib伴随诊断非NGS测试中)，而其余22％的人被表征为非规范突变（仅通过NGS测试可识别）。在6.1%中检测到ESR1突变,在转移样本中表现出更高的频率(15.1%对1.3%，p=0.003)。此外,在3.9%的病例中发现了BRCA1、BRCA2或PALB2的突变，而ERBB2突变的发生率为2.1%。未检测到PTEN突变,也不是TMB高或MSI病例。
■我们描述了巴西ER+/HER2-MBC患者的基因组景观，其中体细胞突变谱与全球文献中描述的相当。这些数据对于在这种情况下制定精准医疗策略非常重要，以及卫生系统管理和研究计划。
■我们使用实验室数据进行了回顾性观察研究（OC精准医学）。我们的研究包括ER+/HER2-MBC患者的肿瘤样本，这些患者从2020年到2023年接受了常规肿瘤检测，并且起源于Oncoclinicas网络内的几个巴西中心。使用了两种不同的下一代测序（NGS）测定：GSFocus（23个基因，涵盖PIK3CA，AKT1，ESR1，ERBB2，BRCA1，BRCA2，PALB2，TP53，但不是PTEN）或GS180（180个基因，包括PTEN,肿瘤突变负荷[TMB]和微卫星不稳定性[MSI])。
■对328名患者的肿瘤样本进行评估，大部分（75.6%）与GSFocus。其中,69%为原发肿瘤,而31%为转移性病灶。PI3K-AKT通路突变的患病率为39.3%(95%置信区间,33%至43%），在PIK3CA中分布为37.5%，在AKT1中分布为1.8%。按年龄分层显示，在50岁以上的患者中，该通路突变的发生率更高（44.5%vs29.1%，p=0.01)。在PIK3CA突变中，78%是规范的(包括在alpelisib伴随诊断非NGS测试中)，而其余22％的人被表征为非规范突变（仅通过NGS测试可识别）。在6.1%中检测到ESR1突变,在转移样本中表现出更高的频率(15.1%对1.3%，p=0.003)。此外,在3.9%的病例中发现了BRCA1、BRCA2或PALB2的突变，而ERBB2突变的发生率为2.1%。未检测到PTEN突变,也不是TMB高或MSI病例。
■我们描述了巴西ER+/HER2-MBC患者的基因组景观，其中体细胞突变谱与全球文献中描述的相当。这些数据对于在这种情况下制定精准医疗策略非常重要，以及卫生系统管理和研究计划。
