Abstract
The intestinal microbiome shapes immune responses and is associated with patient outcomes in cancer following immunotherapy. We evaluated differences between the intestinal microbiome profiles of patients with early-stage invasive breast cancer (BC) and ductal carcinoma in situ (DCIS) by subtype using whole genome metagenomic sequencing. There were no significant differences in microbiome composition between DCIS and invasive BC as measured by alpha diversity (p = 0.20, ANOVA) or beta diversity (p = 0.52, PERMANOVA). Within invasive BC, patients with hormone receptor-positive (HR + )/HER2 + BC differed significantly in beta diversity relative to other subtypes (p < 0.05), with differences in six species (q < 0.25). Bacteroides ovatus was significantly more abundant in patients with stage III BC vs. stage I (p = 0.0003). Functional pathway analysis using HUMAnN3 revealed stage-specific enrichment of amino acid biosynthesis and nucleotide-related pathways. Altogether, these findings highlight potential microbial signatures associated with BC subtype and stage.
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Data availability
Sequencing data for this project are deposited at the NCBI Sequencing Read Archive (SRA) under BioProject PRJNA1295573.
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Acknowledgements
This study was funded by the following sponsors: Lori and Randy Benderson; Elaine and Eduardo Saverin Foundation; Massachusetts Life Sciences Center (to SMT); Merck; MacroGenics; and National Cancer Institute (NCI) Breast Cancer SPORE (P50CA168504). The funders played no role in study design, data collection, analysis and interpretation of data, or the writing of this manuscript.The authors wish to thank Timothy K. Erick, PhD, for medical writing support, Joanna Baginska, PhD for reviewing and providing feedback on the manuscript, and Valerie Hope Goldstein for medical editing and submission support.The authors also wish to thank clinical research coordinators Eileen Wrabel, Jillian Alberti, Ashley Root, and Stefan Atanasov.
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Conceptualization: S.T., E.M., M.H., R.B., A.W., I.S., J.L., and A.G.C. Data curation: S.S., T.K., M.L., X.M., A.M., M.H., T.R., E.R.O., J.G., and S.R. Formal Analysis: X.M., T.K., S.S., and S.T. Funding acquisition: S.T. Investigation: All authorsMethodology: S.T., X.M., T.K., and S.S. Supervision: S.T. and X.M. Writing – original draft: S.S. Writing – review & editing: All authors.
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S.S. reports serving as a consultant for and/or on the advisory boards of AstraZeneca, Daiichi Sankyo, Gilead Sciences, Lilly, Novartis, Pfizer, Incyclix, Sermonix, and Seagen; and research funding from Alterome, Daiichi Sankyo, Iambic, Stemline/Menarini, Pfizer, Seagen, Sermonix, and Relay Therapeutics. N.U.L. declares institutional research support from Genentech, Pfizer, Merck, Seattle Genetics, Zion Pharmaceuticals, Olema Pharmaceuticals, and AstraZeneca; consulting honoraria from Seattle Genetics, Daiichi-Sankyo, AstraZeneca, Olema Pharmaceuticals, Stemline/Menarini, Artera Inc., Eisai, Shorla Oncology, Pfizer, and Denali Therapeutics; royalties from UptoDate (book); and travel support from Olema, AstraZeneca, and DSI. A.G.W. declares research funding to the institution from Gilead, Genentech, Macrogenics, and Merck; serving on the steering committee of AMBRX; and serving as a consultant and paid speaker for AstraZeneca. A.G.-C. declares research funding to institution from Gilead Sciences, AstraZeneca, Daiichi- Sankyo, Merck, Zenith Epigenetics, Bristol-Myers Squibb, Novartis, Biovica, Foundation Medicine, 4D Path, Precede Biosciences, and Bicycle Therapeutics; scientific advisory board service/consulting for AstraZeneca, Daiichi-Sankyo, Novartis, Pfizer, and Gilead Sciences; serving as a speaker for/honoraria from AstraZeneca, Daiichi-Sankyo, Gilead Sciences, and Roche/Genentech; and travel/other support from Roche/Genentech, Gilead Sciences, AstraZeneca, Daiichi Sankyo, Novartis, and Merck. E.A.M. reports compensated service on scientific advisory boards for AstraZeneca, BioNTech, Merck and Moderna; uncompensated service on steering committees for Bristol Myers Squibb and Roche/Genentech; speakers honoraria and travel support from Merck Sharp & Dohme; and institutional research support from Roche/Genentech (via SU2C grant) and Gilead. E.A.M. also reports research funding from Susan Komen for the Cure for which she serves as a Scientific Advisor, and uncompensated participation as a member of the American Society of Clinical Oncology Board of Directors. S.M.T. reports consulting or advisory roles for Novartis, Pfizer/Seagen, Merck, Eli Lilly, AstraZeneca, Genentech/Roche, Eisai, Bristol Myers Squibb/Systimmune, Daiichi Sankyo, Gilead, Blueprint Medicines, Reveal Genomics, Sumitovant Biopharma, Artios Pharma, Menarini/Stemline, Aadi Bio, Bayer, Jazz Pharmaceuticals, Natera, Tango Therapeutics, eFFECTOR, Hengrui USA, Cullinan Oncology, Circle Pharma, Arvinas, BioNTech, Launch Therapeutics, Zuellig Pharma, Johnson&Johnson/Ambrx, Bicycle Therapeutics, BeiGene Therapeutics, Mersana, Summit Therapeutics, Avenzo Therapeutics, Aktis Oncology, Celcuity, Boehringer Ingelheim, Samsung Bioepis, Olema Pharmaceuticals, Tempus, Boundless Bio, and Denali Therapeutics; research funding from Genentech/Roche, Merck, Exelixis, Pfizer, Lilly, Novartis, Bristol Myers Squibb, AstraZeneca, NanoString Technologies, Gilead, Seagen, OncoPep, Daiichi Sankyo, Menarini/Stemline, Jazz Pharmaceuticals, and Olema Pharmaceuticals; and travel support from Lilly, Gilead, Jazz Pharmaceuticals, Pfizer, Arvinas, and Roche. The remaining authors declare no conflicts of interest.
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This study was presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting held May 31-June 4, 2024 in Chicago, IL.
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Sammons, S.L., Kuntz, T.M., DiLullo, M. et al. The landscape of the intestinal microbiome among patients with newly diagnosed invasive breast cancer and ductal carcinoma in situ (DCIS). npj Breast Cancer (2026). https://doi.org/10.1038/s41523-026-00922-3
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DOI: https://doi.org/10.1038/s41523-026-00922-3
