Profiling the gut and oral microbiota of hormone receptor-positive, HER2-negative metastatic breast cancer patients receiving pembrolizumab and eribulin

<b>Aim:</b> Changes in host-associated microbial communities (i.e., the microbiota) may modulate responses to checkpoint blockade immunotherapy. In the KELLY phase II study (NCT03222856), we previously demonstrated that pembrolizumab [anti-programmed cell death protein 1 (PD-1)] combined with eribulin (plus microtubule-targeting chemotherapy) showed encouraging antitumor activity in patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (mBC) who had received prior treatments. <b>Methods:</b> A total of 58 fecal and 67 saliva samples were prospectively collected from a subset of 28 patients at baseline (BL), after three treatment cycles, and end of treatment. Shotgun metagenomics, 16S rRNA gene amplicon sequencing, and bioinformatics and statistical approaches were used to characterize fecal and oral microbiota profiles. <b>Results:</b> Treatment caused no substantial perturbations in gut or oral microbiota, suggesting minimal drug-related microbial toxicity. <i>Bacteroides</i> and <i>Faecalibacterium</i> were the dominant gut microbiota genera, while <i>Prevotella</i> and <i>Streptococcus</i> were present in both oral and gut samples, highlighting potential gut-oral microbial interactions. Additionally, clinical benefit (CB) appeared to be associated with gut-associated <i>Bacteroides fragilis</i> (<i>B. fragilis</i>) and a BL oral abundance of <i>Streptococcus</i> ≥ 30%. Notably, <i>B. fragilis</i> NCTC 9343 supernatant induced dose-dependent lactate dehydrogenase (LDH) release from the MCF-7 (HR-positive/HER2-negative) BC cell line. <b>Conclusion:</b> These findings suggest that specific gut and oral microbiota may modulate the effectiveness of combinatory anti-BC therapies, potentially through the action of microbial metabolites.

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Journal
Microbiome Research Reports
Published
2024-10-31
DOI
https://doi.org/10.20517/mrr.2024.49
Citations
1
Primary Topic
Gut microbiota and health
Type
article
Field-Weighted Citation Impact
0.23

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article

Profiling the gut and oral microbiota of hormone receptor-positive, HER2-negative metastatic breast cancer patients receiving pembrolizumab and eribulin

Giuseppe Curigliano, Nancy M. Y. Teng, Begoña Bermejo, David Seki et al.
1 citations
Microbiome Research Reports
Gut microbiota and health
0.23
article

Profiling the gut and oral microbiota of hormone receptor-positive, HER2-negative metastatic breast cancer patients receiving pembrolizumab and eribulin

Giuseppe Curigliano, Nancy M. Y. Teng, Begoña Bermejo, David Seki, Stephen D. Robinson, Antonio Llombart‐Cussac, María Gión, Mario Mancino, Lindsay J. Hall, Javier Cortés, José Rodríguez-Morató, Tim Robinson, Raymond Kiu, Andrea Malfettone, Romualdo Barroso‐Sousa, Raúl Márquez Vázquez, Leonardo Mina, Aleix Prat, José Manuel Pérez-García, Matthew J. Dalby, Peter Schmid, Eileen Shimizu
article en
1 citations

Abstract

<b>Aim:</b> Changes in host-associated microbial communities (i.e., the microbiota) may modulate responses to checkpoint blockade immunotherapy. In the KELLY phase II study (NCT03222856), we previously demonstrated that pembrolizumab [anti-programmed cell death protein 1 (PD-1)] combined with eribulin (plus microtubule-targeting chemotherapy) showed encouraging antitumor activity in patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (mBC) who had received prior treatments. <b>Methods:</b> A total of 58 fecal and 67 saliva samples were prospectively collected from a subset of 28 patients at baseline (BL), after three treatment cycles, and end of treatment. Shotgun metagenomics, 16S rRNA gene amplicon sequencing, and bioinformatics and statistical approaches were used to characterize fecal and oral microbiota profiles. <b>Results:</b> Treatment caused no substantial perturbations in gut or oral microbiota, suggesting minimal drug-related microbial toxicity. <i>Bacteroides</i> and <i>Faecalibacterium</i> were the dominant gut microbiota genera, while <i>Prevotella</i> and <i>Streptococcus</i> were present in both oral and gut samples, highlighting potential gut-oral microbial interactions. Additionally, clinical benefit (CB) appeared to be associated with gut-associated <i>Bacteroides fragilis</i> (<i>B. fragilis</i>) and a BL oral abundance of <i>Streptococcus</i> ≥ 30%. Notably, <i>B. fragilis</i> NCTC 9343 supernatant induced dose-dependent lactate dehydrogenase (LDH) release from the MCF-7 (HR-positive/HER2-negative) BC cell line. <b>Conclusion:</b> These findings suggest that specific gut and oral microbiota may modulate the effectiveness of combinatory anti-BC therapies, potentially through the action of microbial metabolites.

Microbiome Research ReportsVol. 3(4)
University of East Anglia (GB), Queen Mary University of London (GB), University of Milan (IT), Quadram Institute (GB), University of Bristol (GB), Hospital Clínico Universitario de Valencia (ES), MedSIR (Spain) (ES), Hospital Clínic de Barcelona (ES), Hospital Arnau de Vilanova (ES), Leibniz-Institute for Food Systems Biology at the Technical University of Munich (DE), Hospital Sírio-Libanês (BR), International Breast Cancer Study Group (CH), INCLIVA Health Research Institute (ES), MD Anderson Cancer Center Madrid (ES), Hospital Universitario Ramón y Cajal (ES), European Institute of Oncology (IT), University of Birmingham (GB), Universidad Europea de Madrid (ES)
Biotechnology and Biological Sciences Research Council
Good health and well-being
Openalex Percentile: Top 41%
Gut microbiota and health
0.23
DOIOpen Access PDFOpenAlex
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