Division of Hematology-Oncology, Department of Internal Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, Texas, United States of America.
Division of Biostatistics & Epidemiology, Department of Molecular and Translational Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, Texas, United States of America.
PLoS One. 2020 Sep 4;15(9):e0238262. doi: 10.1371/journal.pone.0238262. eCollection 2020.
Triple-negative breast cancer (TNBC) represents 15%-20% of all breast cancer types. It is more common among African American (AA) and Hispanic-Latina (HL) women. The biology of TNBC in HL women has been poorly characterized, but some data suggest that the molecular drivers of breast cancer might differ. There are no clinical tools to aid medical oncologists with decisions regarding appropriate individualized therapy, and no way to predict long-term outcomes. The aim of this study was to characterize individual patient gene mutation profiles and to identify the relationship with clinical outcomes. We collected formalin-fixed paraffin-embedded tumors (FFPE) from women with TNBC. We analyzed the gene mutation profiles of the collected tumors and compared the results with individual patient's clinical histories and outcomes. Of 25 patients with TNBC, 24 (96%) identified as HL. Twenty-one (84%) had stage III-IV disease. The most commonly mutated genes were TP53, NOTCH1, NOTCH2, NOTCH3, AKT, MEP3K, PIK3CA, and EGFR. Compared with other international cancer databases, our study demonstrated statistically significant higher frequencies of these genes among HL women. Additionally, a worse clinical course was observed among patients whose tumors had mutations in NOTCH genes and PIK3CA. This study is the first to identify the most common genetic alterations among HL women with TNBC. Our data strongly support the notion that molecular drivers of breast cancer could differ in HL women compared with other ethnic backgrounds. Therefore, a deeper understanding of the biological mechanisms behind NOTCH gene and PIK3CA mutations may lead to a new treatment approach.
三阴性乳腺癌(TNBC)占所有乳腺癌类型的 15%-20%。它在非裔美国人和西班牙裔-拉丁裔(HL)女性中更为常见。HL 女性中 TNBC 的生物学特性尚未得到充分描述,但有一些数据表明乳腺癌的分子驱动因素可能不同。目前没有临床工具可以帮助肿瘤内科医生做出关于适当个体化治疗的决策,也无法预测长期结果。本研究的目的是描述个体患者的基因突变谱,并确定与临床结果的关系。我们从患有 TNBC 的女性中收集了福尔马林固定石蜡包埋(FFPE)肿瘤。我们分析了收集肿瘤的基因突变谱,并将结果与个体患者的临床病史和结果进行了比较。在 25 名患有 TNBC 的患者中,24 名(96%)被确定为 HL。21 名(84%)患有 III-IV 期疾病。最常见的突变基因是 TP53、NOTCH1、NOTCH2、NOTCH3、AKT、MEP3K、PIK3CA 和 EGFR。与其他国际癌症数据库相比,我们的研究表明,这些基因在 HL 女性中的频率明显更高。此外,在肿瘤中存在 NOTCH 基因和 PIK3CA 突变的患者中,观察到更差的临床病程。本研究首次确定了 HL 女性中 TNBC 最常见的遗传改变。我们的数据强烈支持这样一种观点,即与其他种族背景相比,HL 女性中乳腺癌的分子驱动因素可能不同。因此,深入了解 NOTCH 基因和 PIK3CA 突变背后的生物学机制可能会导致新的治疗方法。