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

Published version
Peer-reviewed

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Authors

Terrisse, Safae 
Derosa, Lisa 
Iebba, Valerio 
Ghiringhelli, François  ORCID logo  https://orcid.org/0000-0002-5465-8305
Vaz-Luis, Ines 

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.

Description

Keywords

Breast Neoplasms, Female, Gastrointestinal Microbiome, Humans, Prognosis, Prospective Studies, Treatment Outcome

Journal Title

Cell Death Differ

Conference Name

Journal ISSN

1350-9047
1476-5403

Volume Title

28

Publisher

Springer Science and Business Media LLC
Sponsorship
European Commission (233655)
European Commission Horizon 2020 (H2020) Societal Challenges (825410)