Effect of estrogen receptor status on circulatory immune and metabolomics profiles of her2-positive breast cancer patients enrolled for neoadjuvant targeted chemotherapy

Alessia Vignoli, Elena Muraro, Gianmaria Miolo, Leonardo Tenori, Paola Turano, Emanuela Di Gregorio, Agostino Steffan, Claudio Luchinat, Giuseppe Corona

Research output: Contribution to journalArticlepeer-review

Abstract

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 and1H 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, p = 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.

Original languageEnglish
Article number314
Number of pages16
JournalCancers
Volume12
Issue number2
DOIs
Publication statusPublished - Feb 2020

Keywords

  • Breast cancer
  • Cytokines
  • Estrogen receptors
  • HER2-positive
  • Metabolomics

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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