Gustave Roussy Cancer Center, Villejuif, France.
INSERM U1015, Equipe Labellisée par la ligue Contre le Cancer, Villejuif, France.
Cell Death Differ. 2021 Sep;28(9):2778-2796. doi: 10.1038/s41418-021-00784-1. Epub 2021 May 7.
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.
早期乳腺癌(BC)的预后依赖于细胞自主和免疫参数。肠道微生物组对临床结果的影响尚未得到评估。使用 shotgun 宏基因组学来确定 76 名早期 BC 患者的 121 份粪便样本中的粪便微生物组组成,其中 45 份为化疗前后配对样本。这些患者被纳入 CANTO 前瞻性研究中,旨在记录与 BC 临床管理相关的副作用。我们分析了基线或化疗后粪便微生物组与 BC 预后以及与治疗诱导的副作用之间的关联,同时还在接受 BC 患者微生物组定植的免疫功能正常的小鼠中检验了这些发现的临床相关性,随后这些小鼠受到组织相容性小鼠 BC 和化疗的挑战。我们的结论是,与健康个体相比,在 BC 患者中过度丰富的特定肠道共生菌会对 BC 的预后产生负面影响,受化疗调节,并可能影响 BC 治疗的体重增加和神经副作用。这些在辅助和新辅助环境中获得的发现需要前瞻性验证。
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