Intestinal microbiota influences clinical outcome and side effects of early breast cancer treatment

S. Terrisse, L. Derosa, V. Iebba, F. Ghiringhelli, I. Vaz-Luis, G. Kroemer, M. Fidelle, S. Christodoulidis, N. Segata, A.M. Thomas, A.L. Martin, A. Sirven, S. Everhard, F. Aprahamian, N. Nirmalathasan, R. Aarnoutse, M. Smidt, J. Ziemons, C. Caldas, S. LoiblC. Denkert, S. Durand, C. Iglesias, F. Pietrantonio, B. Routy, F. Andre, E. Pasolli, S. Delaloge, L. Zitvogel*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

20 Citations (Web of Science)

Abstract

The prognosis of early breast cancer (BC) relies on cell autonomous and immune parameters. The impact of the intestinal microbiome on clinical outcome has not yet been evaluated. Shotgun metagenomics was used to determine the composition of the fecal microbiota in 121 specimens from 76 early BC patients, 45 of whom were paired before and after chemotherapy. These patients were enrolled in the CANTO prospective study designed to record the side effects associated with the clinical management of BC. We analyzed associations between baseline or post-chemotherapy fecal microbiota and plasma metabolomics with BC prognosis, as well as with therapy-induced side effects. We examined the clinical relevance of these findings in immunocompetent mice colonized with BC patient microbiota that were subsequently challenged with histo-compatible mouse BC and chemotherapy. We conclude that specific gut commensals that are overabundant in BC patients compared with healthy individuals negatively impact BC prognosis, are modulated by chemotherapy, and may influence weight gain and neurological side effects of BC therapies. These findings obtained in adjuvant and neoadjuvant settings warrant prospective validation.
Original languageEnglish
Pages (from-to)2778-2796
Number of pages19
JournalCell Death and Differentiation
Volume28
Issue number9
DOIs
Publication statusPublished - 1 Sep 2021

Keywords

  • TUMOR-INFILTRATING LYMPHOCYTES
  • STANDARDIZED METHOD
  • GUT MICROBIOME
  • SOLID TUMORS
  • ADENOSINE
  • IMMUNOTHERAPY
  • EFFICACY
  • THERAPY
  • PATHOLOGISTS
  • CARCINOMA

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