TY - JOUR
T1 - Intestinal microbiota influences clinical outcome and side effects of early breast cancer treatment
AU - Terrisse, Safae
AU - Derosa, Lisa
AU - Iebba, Valerio
AU - Ghiringhelli, François
AU - Vaz-Luis, Ines
AU - Kroemer, Guido
AU - Fidelle, Marine
AU - Christodoulidis, Stergios
AU - Segata, Nicola
AU - Thomas, Andrew Maltez
AU - Martin, Anne Laure
AU - Sirven, Aude
AU - Everhard, Sibille
AU - Aprahamian, Fanny
AU - Nirmalathasan, Nitharsshini
AU - Aarnoutse, Romy
AU - Smidt, Marjolein
AU - Ziemons, Janine
AU - Caldas, Carlos
AU - Loibl, Sibylle
AU - Denkert, Carsten
AU - Durand, Sylvere
AU - Iglesias, Claudia
AU - Pietrantonio, Filippo
AU - Routy, Bertrand
AU - André, Fabrice
AU - Pasolli, Edoardo
AU - Delaloge, Suzette
AU - Zitvogel, Laurence
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/9/1
Y1 - 2021/9/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85105426285&partnerID=8YFLogxK
U2 - 10.1038/s41418-021-00784-1
DO - 10.1038/s41418-021-00784-1
M3 - Article
C2 - 33963313
AN - SCOPUS:85105426285
SN - 1350-9047
VL - 28
SP - 2778
EP - 2796
JO - Cell Death and Differentiation
JF - Cell Death and Differentiation
IS - 9
ER -