{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T11:27:47Z","timestamp":1770722867153,"version":"3.49.0"},"reference-count":112,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,3,16]],"date-time":"2022-03-16T00:00:00Z","timestamp":1647388800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Breast cancer is classified into four major molecular subtypes, and is considered a heterogenous disease. The risk profiles and treatment of breast cancer differ according to these subtypes. Early detection dramatically improves the prospects of successful treatment, resulting in a reduction in overall mortality rates. However, almost 30% of women primarily diagnosed with the early-stage disease will eventually develop metastasis or resistance to chemotherapies. Immunotherapies are among the most promising cancer treatment options; however, long-term clinical benefit has only been observed in a small subset of responding patients. The current strategies for diagnosis and treatment rely heavily on histopathological examination and molecular diagnosis, disregarding the tumor microenvironment and microbiome involving cancer cells. In this review, we aim to praise the use of pharmacogenomics and pharmacomicrobiomics as a strategy to identify potential biomarkers for guiding and monitoring therapy in real-time. The finding of these biomarkers can be performed by studying the metabolism of drugs, more specifically, immunometabolism, and its relationship with the microbiome, without neglecting the information provided by genetics. A larger understanding of cancer biology has the potential to improve patient care, enable clinical decisions, and deliver personalized medicine.<\/jats:p>","DOI":"10.3390\/ijms23063181","type":"journal-article","created":{"date-parts":[[2022,3,16]],"date-time":"2022-03-16T03:34:13Z","timestamp":1647401653000},"page":"3181","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Drug Metabolism for the Identification of Clinical Biomarkers in Breast Cancer"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2434-5874","authenticated-orcid":false,"given":"B\u00e1rbara","family":"Costa","sequence":"first","affiliation":[{"name":"OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Dr. Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1283-1042","authenticated-orcid":false,"given":"Nuno","family":"Vale","sequence":"additional","affiliation":[{"name":"OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Dr. Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"},{"name":"Department of Community Medicine, Health Information and Decision (MEDCIDS), Faculty of Medicine, University of Porto, Al. Prof. Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"Associate Laboratory RISE-Health Research Network, Faculty of Medicine, University of Porto, Al. Prof. Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.molonc.2010.04.004","article-title":"Histological types of breast cancer: How special are they?","volume":"4","author":"Weigelt","year":"2010","journal-title":"Mol. Oncol."},{"key":"ref_3","first-page":"1864","article-title":"Breast cancer molecular subtypes: From TNBC to QNBC","volume":"6","author":"Hon","year":"2016","journal-title":"Am. J. Cancer Res."},{"key":"ref_4","first-page":"540","article-title":"Hormone receptors in breast cancer: More than estrogen receptors","volume":"79","author":"Lamb","year":"2019","journal-title":"Medicina"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Early Breast Cancer Trialists\u2019 Collaborative Group (EBCTCG) (2015). Aromatase inhibitors versus tamoxifen in early breast cancer: Patient-level meta-analysis of the randomised trials. Lancet, 386, 1341\u20131352.","DOI":"10.1016\/S0140-6736(15)61074-1"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e168","DOI":"10.3747\/co.25.3735","article-title":"Aromatase Inhibitors in Premenopausal Women with Breast Cancer: The State of the Art and Future Prospects","volume":"25","author":"Pistelli","year":"2018","journal-title":"Curr. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/s41571-019-0268-3","article-title":"HER2-targeted therapies\u2014A role beyond breast cancer","volume":"17","author":"Oh","year":"2020","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Lee, J.S., Yost, S.E., and Yuan, Y. (2020). Neoadjuvant Treatment for Triple Negative Breast Cancer: Recent Progresses and Challenges. Cancers, 12.","DOI":"10.3390\/cancers12061404"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"113265","DOI":"10.1016\/j.jpba.2020.113265","article-title":"Monitoring of drug resistance towards reducing the toxicity of pharmaceutical compounds: Past, present and future","volume":"186","author":"Ahmadian","year":"2020","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Henriques, B., Mendes, F., and Martins, D. (2021). Immunotherapy in Breast Cancer: When, How, and What Challenges?. Biomedicines, 9.","DOI":"10.3390\/biomedicines9111687"},{"key":"ref_11","first-page":"1045","article-title":"The trastuzumab era: Current and upcoming targeted HER2+ breast cancer therapies","volume":"10","author":"Kreutzfeldt","year":"2020","journal-title":"Am. J. Cancer Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1178223418774802","DOI":"10.1177\/1178223418774802","article-title":"Breast Cancer Immunotherapy: An Update","volume":"12","author":"Makhoul","year":"2018","journal-title":"Breast Cancer Basic Clin. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1208\/s12248-020-00514-4","article-title":"Identification and Utilization of Biomarkers to Predict Response to Immune Checkpoint Inhibitors","volume":"22","author":"Gjoerup","year":"2020","journal-title":"AAPS J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1002\/cam4.3550","article-title":"Predictive Biomarkers for Immune Checkpoint Inhibitors in Metastatic Breast Cancer","volume":"10","author":"Sivapiragasam","year":"2021","journal-title":"Cancer Med."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Tower, H., Ruppert, M., and Britt, K. (2019). The Immune Microenvironment of Breast Cancer Progression. Cancers, 11.","DOI":"10.3390\/cancers11091375"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"284","DOI":"10.3389\/fonc.2018.00284","article-title":"Metabolic Switch in the Tumor Microenvironment Determines Immune Responses to Anti-cancer Therapy","volume":"8","author":"Wegiel","year":"2018","journal-title":"Front. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"348","DOI":"10.3389\/fimmu.2019.00348","article-title":"Immune Tumor Microenvironment in Breast Cancer and the Participation of Estrogen and Its Receptors in Cancer Physiopathology","volume":"10","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1007\/s10549-020-05771-7","article-title":"Tumor-infiltrating lymphocytes (TILs) in ER+\/HER2\u2212 breast cancer","volume":"183","author":"Criscitiello","year":"2020","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1007\/s11523-016-0451-8","article-title":"Prognostic Role of Programmed Death Ligand-1 Expression in Breast Cancer: A Systematic Review and Meta-Analysis","volume":"11","author":"Li","year":"2016","journal-title":"Target. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1038\/nrclinonc.2015.215","article-title":"Clinical relevance of host immunity in breast cancer: From TILs to the clinic","volume":"13","author":"Savas","year":"2016","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.3390\/cancers7040902","article-title":"Cancer-Associated Fibroblasts: Their Characteristics and Their Roles in Tumor Growth","volume":"7","author":"Shiga","year":"2015","journal-title":"Cancers"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"S\u00fckei, T., Palma, E., and Urbani, L. (2021). Interplay between Cellular and Non-Cellular Components of the Tumour Microenvironment in Hepatocellular Carcinoma. Cancers, 13.","DOI":"10.3390\/cancers13215586"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.clim.2019.02.007","article-title":"Cytokines, growth factors and proteases in medium and large vessel vasculitis","volume":"206","author":"Weyand","year":"2019","journal-title":"Clin. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"6345","DOI":"10.1002\/jcp.29668","article-title":"Breast cancer-derived exosomes: Tumor progression and therapeutic agents","volume":"235","author":"Jabbari","year":"2020","journal-title":"J. Cell. Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"221","DOI":"10.3389\/fonc.2020.00221","article-title":"Resistance Mechanisms to Anti-angiogenic Therapies in Cancer","volume":"10","author":"Haibe","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.tibs.2015.12.001","article-title":"The Warburg Effect: How Does it Benefit Cancer Cells?","volume":"41","author":"Liberti","year":"2016","journal-title":"Trends Biochem. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"104511","DOI":"10.1016\/j.phrs.2019.104511","article-title":"Targeting glucose metabolism to suppress cancer progression: Prospective of anti-glycolytic cancer therapy","volume":"150","author":"Mahmoud","year":"2019","journal-title":"Pharmacol. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.cell.2016.05.035","article-title":"Mitochondrial Dynamics Controls T Cell Fate through Metabolic Programming","volume":"166","author":"Buck","year":"2016","journal-title":"Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/imr.12858","article-title":"Immunometabolism: From basic mechanisms to translation","volume":"295","author":"Makowski","year":"2020","journal-title":"Immunol. Rev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.cell.2017.08.018","article-title":"Mitochondrial Priming by CD28","volume":"171","author":"Geltink","year":"2017","journal-title":"Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1038\/s41423-021-00833-2","article-title":"Microenvironmental influences on T cell immunity in cancer and inflammation","volume":"19","author":"Heintzman","year":"2022","journal-title":"Cell. Mol. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"106550","DOI":"10.1016\/j.yebeh.2019.106550","article-title":"Mechanistic target of rapamycin (mTOR) signaling in status epilepticus","volume":"101","author":"Crino","year":"2019","journal-title":"Epilepsy Behav."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Mik\u00f3, E., Kov\u00e1cs, T., Seb\u0151, \u00c9., T\u00f3th, J., Csonka, T., Ujlaki, G., Sipos, A., Szab\u00f3, J., M\u00e9hes, G., and Bai, P. (2019). Microbiome\u2014Microbial Metabolome\u2014Cancer Cell Interactions in Breast Cancer\u2014Familiar, but Unexplored. Cells, 8.","DOI":"10.3390\/cells8040293"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"He, L., Wick, N., Germans, S.K., and Peng, Y. (2021). The Role of Breast Cancer Stem Cells in Chemoresistance and Metastasis in Triple-Negative Breast Cancer. Cancers, 13.","DOI":"10.3390\/cancers13246209"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1007\/s13277-013-0707-1","article-title":"Metabolic phenotypes in triple-negative breast cancer","volume":"34","author":"Kim","year":"2013","journal-title":"Tumor Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s40170-017-0168-x","article-title":"Metabolic profiling of triple-negative breast cancer cells reveals metabolic vulnerabilities","volume":"5","author":"Lanning","year":"2017","journal-title":"Cancer Metab."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Gandhi, N., and Das, G.M. (2019). Metabolic Reprogramming in Breast Cancer and Its Therapeutic Implications. Cells, 8.","DOI":"10.3390\/cells8020089"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.drup.2018.03.001","article-title":"How the Warburg effect supports aggressiveness and drug resistance of cancer cells?","volume":"38","author":"Icard","year":"2018","journal-title":"Drug Resist. Updates"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1038\/msb.2012.25","article-title":"The glucose-deprivation network counteracts lapatinib-induced toxicity in resistant ErbB2-positive breast cancer cells","volume":"8","author":"Komurov","year":"2012","journal-title":"Mol. Syst. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"4585","DOI":"10.1158\/0008-5472.CAN-11-0127","article-title":"Overcoming Trastuzumab Resistance in Breast Cancer by Targeting Dysregulated Glucose Metabolism","volume":"71","author":"Zhao","year":"2011","journal-title":"Cancer Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/1476-4598-9-33","article-title":"Warburg effect in chemosensitivity: Targeting lactate dehydrogenase-A re-sensitizes Taxol-resistant cancer cells to Taxol","volume":"9","author":"Zhou","year":"2010","journal-title":"Mol. Cancer"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Kalezic, A., Udicki, M., Galic, B.S., Aleksic, M., Korac, A., Jankovic, A., and Korac, B. (2020). Lactate Metabolism in Breast Cancer Microenvironment: Contribution Focused on Associated Adipose Tissue and Obesity. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21249676"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"12156","DOI":"10.1038\/ncomms12156","article-title":"ERR\u03b1 mediates metabolic adaptations driving lapatinib resistance in breast cancer","volume":"7","author":"Deblois","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"20309","DOI":"10.18632\/oncotarget.15852","article-title":"Mitochondrial \u201cpower\u201d drives tamoxifen resistance: NQO1 and GCLC are new therapeutic targets in breast cancer","volume":"8","author":"Fiorillo","year":"2017","journal-title":"Oncotarget"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1158\/1535-7163.MCT-07-0445","article-title":"A new mechanism of drug resistance in breast cancer cells: Fatty acid synthase overexpression-mediated palmitate overproduction","volume":"7","author":"Liu","year":"2008","journal-title":"Mol. Cancer Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1142\/S2339547818300020","article-title":"The growing role of precision and personalized medicine for cancer treatment","volume":"6","author":"Krzyszczyk","year":"2018","journal-title":"Technology"},{"key":"ref_47","first-page":"62","article-title":"Trastuzumab: Updated mechanisms of action and resistance in breast cancer","volume":"2","author":"Claret","year":"2012","journal-title":"Front. Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.semcancer.2017.08.010","article-title":"Prognostic and predictive biomarkers in breast cancer: Past, present and future","volume":"52","author":"Nicolini","year":"2018","journal-title":"Semin. Cancer Biol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Wu, H.-J., and Chu, P.-Y. (2021). Recent Discoveries of Macromolecule- and Cell-Based Biomarkers and Therapeutic Implications in Breast Cancer. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22020636"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1111\/joim.12084","article-title":"Breast cancer as a systemic disease: A view of metastasis","volume":"274","author":"Redig","year":"2013","journal-title":"J. Intern. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1038\/s41416-019-0663-7","article-title":"Defining a metabolic landscape of tumours: Genome meets metabolism","volume":"122","author":"Nanda","year":"2020","journal-title":"Br. J. Cancer"},{"key":"ref_52","first-page":"59","article-title":"Personalized medicine in breast cancer: Pharmacogenomics approaches","volume":"12","author":"Jeibouei","year":"2019","journal-title":"Pharm. Pers. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e226","DOI":"10.1002\/cpz1.226","article-title":"PharmGKB, an Integrated Resource of Pharmacogenomic Knowledge","volume":"1","author":"Gong","year":"2021","journal-title":"Curr. Protoc."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/aps.2014.123","article-title":"Identification of estrogen-responsive genes based on the DNA binding properties of estrogen receptors using high-throughput sequencing technology","volume":"36","author":"Ikeda","year":"2015","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3645","DOI":"10.1158\/0008-5472.CAN-18-0430","article-title":"HER2 Amplification in Tumors Activates PI3K\/Akt Signaling Independent of HER3","volume":"78","author":"Dreyer","year":"2018","journal-title":"Cancer Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.2174\/1871530320666200428113051","article-title":"MicroRNAs as Biomarker for Breast Cancer","volume":"20","author":"Aggarwal","year":"2020","journal-title":"Endocr. Metab. Immune Disord. Drug Targets"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"106535","DOI":"10.1016\/j.intimp.2020.106535","article-title":"Breast cancer: Biology, biomarkers, and treatments","volume":"84","author":"Barzaman","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s13073-019-0703-1","article-title":"Molecular profiling for precision cancer therapies","volume":"12","author":"Malone","year":"2020","journal-title":"Genome Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.1016\/j.ajpath.2017.04.021","article-title":"The Evolving Role of Companion Diagnostics for Breast Cancer in an Era of Next-Generation Omics","volume":"187","author":"Rosenbaum","year":"2017","journal-title":"Am. J. Pathol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1007\/s40291-020-00482-7","article-title":"Oncotype DX Breast Recurrence Score\u00ae: A Review of its Use in Early-Stage Breast Cancer","volume":"24","author":"Syed","year":"2020","journal-title":"Mol. Diagn. Ther."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Soliman, H., Shah, V., Srkalovic, G., Mahtani, R., Levine, E., Mavromatis, B., Srinivasiah, J., Kassar, M., Gabordi, R., and Qamar, R. (2020). MammaPrint guides treatment decisions in breast Cancer: Results of the IMPACt trial. BMC Cancer, 20.","DOI":"10.1186\/s12885-020-6534-z"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Davey, M.G., Hynes, S.O., Kerin, M.J., Miller, N., and Lowery, A.J. (2021). Ki-67 as a Prognostic Biomarker in Invasive Breast Cancer. Cancers, 13.","DOI":"10.3390\/cancers13174455"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Hwang, S. (2012). Comparison and evaluation of pathway-level aggregation methods of gene expression data. BMC Genom., 13.","DOI":"10.1186\/1471-2164-13-S7-S26"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Greenblum, S.I., Efroni, S., Schaefer, C.F., and Buetow, K.H. (2011). The PathOlogist: An automated tool for pathway-centric analysis. BMC Bioinform., 12.","DOI":"10.1186\/1471-2105-12-133"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.semcancer.2018.06.003","article-title":"Molecular pathway activation\u2014New type of biomarkers for tumor morphology and personalized selection of target drugs","volume":"53","author":"Buzdin","year":"2018","journal-title":"Semin. Cancer Biol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1007\/s11481-009-9156-4","article-title":"Metabolomics: Moving to the Clinic","volume":"5","author":"Lewensohn","year":"2010","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1038\/nrm.2016.25","article-title":"Metabolomics: Beyond biomarkers and towards mechanisms","volume":"17","author":"Johnson","year":"2016","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Ward, T., Larson, J., Meulemans, J., Hillmann, B., Lynch, J., Sidiropoulos, D., Spear, J.R., Caporaso, G., Blekhman, R., and Knight, R. (2017). BugBase predicts organism-level microbiome phenotypes. bioRxiv, 133462.","DOI":"10.1101\/133462"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Douglas, G.M., Maffei, V.J., Zaneveld, J., Yurgel, S.N., Brown, J.R., Taylor, C.M., Huttenhower, C., and Langille, M.G.I. (2019). PIC-RUSt2: An improved and customizable approach for metagenome inference. bioRxiv, 672295.","DOI":"10.1101\/672295"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1038\/s41587-019-0209-9","article-title":"Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2","volume":"37","author":"Bolyen","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1186\/s12885-021-08664-0","article-title":"The role of the bacterial microbiome in the treatment of cancer","volume":"21","author":"Yu","year":"2021","journal-title":"BMC Cancer"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"4841","DOI":"10.7150\/jca.58986","article-title":"Tumor-related Microbiome in the Breast Microenvironment and Breast Cancer","volume":"12","author":"Wang","year":"2021","journal-title":"J. Cancer"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"3007","DOI":"10.1128\/AEM.00242-14","article-title":"Microbiota of Human Breast Tissue","volume":"80","author":"Urbaniak","year":"2014","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/s13073-021-00874-2","article-title":"Human breast microbiome correlates with prognostic features and immunological signatures in breast cancer","volume":"13","author":"Tzeng","year":"2021","journal-title":"Genome Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"28061","DOI":"10.1038\/srep28061","article-title":"Characterization of the microbiome of nipple aspirate fluid of breast cancer survivors","volume":"6","author":"Chan","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Xuan, C., Shamonki, J.M., Chung, A., DiNome, M., Chung, M., Sieling, P.A., and Lee, D.J. (2014). Microbial Dysbiosis Is Associated with Human Breast Cancer. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0083744"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1016\/j.ajpath.2021.02.020","article-title":"Exploring the Potential of Breast Microbiota as Biomarker for Breast Cancer and Therapeutic Response","volume":"191","author":"Dieleman","year":"2021","journal-title":"Am. J. Pathol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"120","DOI":"10.3389\/fonc.2020.00120","article-title":"Microbiome and Breast Cancer: New Role for an Ancient Population","volume":"10","author":"Halvaei","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Bodai, B. (2020). Breast Cancer: Lifestyle, the Human Gut Microbiota\/Microbiome, and Survivorship. Perm. J., 24.","DOI":"10.7812\/TPP\/19.129"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1186\/s40425-019-0574-4","article-title":"Exploring the emerging role of the microbiome in cancer immunotherapy","volume":"7","author":"Fessler","year":"2019","journal-title":"J. Immunother. Cancer"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1080\/19490976.2018.1511665","article-title":"Bugs in the system: Bringing the human microbiome to bear in cancer immunotherapy","volume":"10","author":"Strouse","year":"2019","journal-title":"Gut Microbes"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/s41568-019-0116-x","article-title":"The evolving landscape of biomarkers for checkpoint inhibitor immunotherapy","volume":"19","author":"Havel","year":"2019","journal-title":"Nat. Rev. Cancer"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"17915","DOI":"10.18632\/oncotarget.24681","article-title":"Microbiota effects on cancer: From risks to therapies","volume":"9","author":"Rea","year":"2018","journal-title":"Oncotarget"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"103012","DOI":"10.1016\/j.isci.2021.103012","article-title":"Antibiotic-induced disturbances of the gut microbiota result in accelerated breast tumor growth","volume":"24","author":"McKee","year":"2021","journal-title":"iScience"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"110409","DOI":"10.1016\/j.biopha.2020.110409","article-title":"Probiotics for cancer alternative prevention and treatment","volume":"129","author":"Bedada","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"22","DOI":"10.3402\/fnr.v45i0.1785","article-title":"Safety aspects of probiotic products","volume":"45","author":"Marteau","year":"2001","journal-title":"N\u00e4ringsforskning"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/s41579-020-0433-9","article-title":"Gut microbiota in human metabolic health and disease","volume":"19","author":"Fan","year":"2021","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1128\/CMR.00046-08","article-title":"Pathogen Recognition and Inflammatory Signaling in Innate Immune Defenses","volume":"22","author":"Mogensen","year":"2009","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"a016246","DOI":"10.1101\/cshperspect.a016246","article-title":"Microbial Sensing by Toll-Like Receptors and Intracellular Nucleic Acid Sensors","volume":"7","author":"Pandey","year":"2014","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1038\/cmi.2014.76","article-title":"Amino acids 89\u201396 of Salmonella typhimurium flagellin represent the major domain responsible for TLR5-independent adjuvanticity in the humoral immune response","volume":"12","author":"Zhang","year":"2014","journal-title":"Cell. Mol. Immunol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"11746","DOI":"10.18632\/oncotarget.7459","article-title":"Drug resistance in cancer: Molecular evolution and compensatory proliferation","volume":"7","author":"Friedman","year":"2016","journal-title":"Oncotarget"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/s00280-008-0855-y","article-title":"Irinotecan-induced mucositis is associated with changes in intestinal mucins","volume":"64","author":"Stringer","year":"2009","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1093\/ibd\/izx029","article-title":"A Cross-Talk Between Microbiota-Derived Short-Chain Fatty Acids and the Host Mucosal Immune System Regulates Intestinal Homeostasis and Inflammatory Bowel Disease","volume":"24","year":"2018","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Yoo, J.Y., Groer, M., Dutra, S.V.O., Sarkar, A., and McSkimming, D.I. (2020). Gut Microbiota and Immune System Interactions. Microorganisms, 8.","DOI":"10.3390\/microorganisms8101587"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1038\/nature12726","article-title":"Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation","volume":"504","author":"Arpaia","year":"2013","journal-title":"Nature"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1038\/nature08530","article-title":"Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43","volume":"461","author":"Maslowski","year":"2009","journal-title":"Nature"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/s41392-019-0074-5","article-title":"Demystifying the manipulation of host immunity, metabolism, and extraintestinal tumors by the gut microbiome","volume":"4","author":"Zhang","year":"2019","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.maturitas.2017.06.025","article-title":"Estrogen\u2013gut microbiome axis: Physiological and clinical implications","volume":"103","author":"Baker","year":"2017","journal-title":"Maturitas"},{"key":"ref_99","unstructured":"Kwa, M., Plottel, C.S., Blaser, M.J., and Adams, S. (2016). The Intestinal Microbiome and Estrogen Receptor\u2013Positive Female Breast Cancer. JNCI J. Natl. Cancer Inst., 108."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1186\/1479-5876-10-253","article-title":"Fecal microbial determinants of fecal and systemic estrogens and estrogen metabolites: A cross-sectional study","volume":"10","author":"Flores","year":"2012","journal-title":"J. Transl. Med."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Thirunavukkarasan, M., Wang, C., Rao, A., Hind, T., Teo, Y.R., Siddiquee, A.A.-M., Goghari, M.A.I., Kumar, A.P., and Herr, D.R. (2017). Short-chain fatty acid receptors inhibit invasive phenotypes in breast cancer cells. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0186334"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1007\/164_2016_48","article-title":"Free Fatty Acid Receptors and Cancer: From Nutrition to Pharmacology","volume":"236","author":"Hopkins","year":"2016","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"14706","DOI":"10.1038\/ncomms14706","article-title":"Adipocytes promote malignant growth of breast tumours with monocarboxylate transporter 2 expression via \u03b2-hydroxybutyrate","volume":"8","author":"Huang","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.mam.2017.06.002","article-title":"Interactions between gut bacteria and bile in health and disease","volume":"56","author":"Long","year":"2017","journal-title":"Mol. Asp. Med."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1186\/s13058-014-0415-9","article-title":"A joint analysis of metabolomics and genetics of breast cancer","volume":"16","author":"Tang","year":"2014","journal-title":"Breast Cancer Res."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1194\/jlr.M020313","article-title":"Identification and characterization of two bile acid coenzyme A transferases from Clostridium scindens, a bile acid 7\u03b1-dehydroxylating intestinal bacterium","volume":"53","author":"Ridlon","year":"2012","journal-title":"J. Lipid Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"3389","DOI":"10.1016\/j.jmb.2015.06.020","article-title":"Remaining Mysteries of Molecular Biology: The Role of Polyamines in the Cell","volume":"427","author":"Campbell","year":"2015","journal-title":"J. Mol. Biol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1038\/s41598-018-37664-7","article-title":"Cadaverine, a metabolite of the microbiome, reduces breast cancer aggressiveness through trace amino acid receptors","volume":"9","author":"Vida","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1016\/j.clinthera.2015.04.002","article-title":"Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders with Suspected Immune Dysregulation","volume":"37","author":"Petra","year":"2015","journal-title":"Clin. Ther."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.gtc.2016.09.007","article-title":"The Microbiome-Gut-Brain Axis in Health and Disease","volume":"46","author":"Dinan","year":"2017","journal-title":"Gastroenterol. Clin. N. Am."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1038\/mp.2016.50","article-title":"From gut dysbiosis to altered brain function and mental illness: Mechanisms and pathways","volume":"21","author":"Rogers","year":"2016","journal-title":"Mol. Psychiatry"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s13073-018-0525-6","article-title":"The microbiome in precision medicine: The way forward","volume":"10","author":"Petrosino","year":"2018","journal-title":"Genome Med."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/6\/3181\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:37:13Z","timestamp":1760135833000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/6\/3181"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,16]]},"references-count":112,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["ijms23063181"],"URL":"https:\/\/doi.org\/10.3390\/ijms23063181","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,16]]}}}