Vignoli Alessia, Muraro Elena, Miolo Gianmaria, Tenori Leonardo, Turano Paola, Di Gregorio Emanuela, Steffan Agostino, Luchinat Claudio, Corona Giuseppe
Magnetic Resonance Center (CERM), University of Florence, 50019 Florence, Italy.
Consorzio Interuniversitario Risonanze Magnetiche di Metallo Proteine (C.I.R.M.M.P.), 50019 Sesto Fiorentino, Italy.
Cancers (Basel). 2020 Jan 29;12(2):314. doi: 10.3390/cancers12020314.
HER2-positive breast cancer (BC) represents a heterogeneous cancer disease. In an attempt to identify new stratification models useful for prognosis and therapeutic strategy, we investigated the influence of estrogen receptor (ER) status on the host immune and metabolomics profile of HER2-positive BC patients enrolled for neoadjuvant targeted chemotherapy (NATC). The study enrolled 43 HER2-positive BC patients eligible for NATC based on the trastuzumab-paclitaxel combination. Baseline circulatory cytokines and H NMR plasma metabolomics profiles were investigated. Differences in the immune cytokines and metabolomics profile as a function of the ER status, and their association with clinical outcomes were studied by multivariate and univariate analysis. Baseline metabolomics profiles were found to discriminate HER2-positive ER(+) from ER(-) BC patients. Within the ER(+) group an immune-metabolomics model, based on TNF-α and valine, predicted pathological complete response to NATC with 90.9% accuracy (AUROC = 0.92, = 0.004). Moreover, metabolomics information integrated with IL-2 and IL-10 cytokine levels were prognostic of relapse with an accuracy of 95.5%. The results indicate that in HER2-positive BC patients the ER status influences the host circulatory immune-metabolomics profile. The baseline immune-metabolomics assessment in combination with ER status could represent an independent stratification tool able to predict NATC response and disease relapse of HER2-positive patients.
人表皮生长因子受体2（HER2）阳性乳腺癌（BC）是一种异质性癌症疾病。为了确定有助于预后和治疗策略的新分层模型，我们研究了雌激素受体（ER）状态对接受新辅助靶向化疗（NATC）的HER2阳性BC患者宿主免疫和代谢组学特征的影响。该研究纳入了43例符合曲妥珠单抗-紫杉醇联合方案NATC标准的HER2阳性BC患者。研究了基线循环细胞因子和氢核磁共振血浆代谢组学特征。通过多变量和单变量分析研究了免疫细胞因子和代谢组学特征随ER状态的差异及其与临床结局的关联。发现基线代谢组学特征能够区分HER2阳性ER（+）和ER（-）的BC患者。在ER（+）组中，基于肿瘤坏死因子-α（TNF-α）和缬氨酸的免疫代谢组学模型预测NATC病理完全缓解的准确率为90.9%（曲线下面积=0.92，P=0.004）。此外，结合白细胞介素-2（IL-2）和白细胞介素-10（IL-10）细胞因子水平的代谢组学信息对复发的预测准确率为95.5%。结果表明，在HER2阳性BC患者中，ER状态影响宿主循环免疫代谢组学特征。结合ER状态的基线免疫代谢组学评估可能是一种能够预测HER2阳性患者NATC反应和疾病复发的独立分层工具。
