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Multiple risk factors drive its onset and progression, and current therapies still leave many patients with distant metastases without cure. Extracellular matrix degradation and epithelial–mesenchymal transition are key steps in local invasion, while gut and other microbial communities can shape cancer biology through dysbiosis. 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Breast Cancer: Extracellular Matrix and Microbiome Interactions. Int. J. Mol. Sci. 2024, 25, 7226. [https://](https://)[ ](https://)[doi.org/10.3390/ijms25137226](doi.org/10.3390/ijms25137226)  \nAcademic Editor: Bernard Haendler  \nReceived: 6 June 2024  \nRevised: 26 June 2024  \nAccepted: 28 June 2024  \nPublished: 30 June 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Department of Physiology, Schools of Pharmacy and Medicine, University of Granada, 18071 Granada, Spain; lourdesherrera@ugr.es (L.H.-Q.); hectorvazquez@ugr.es (H.V.-L.)  \n2 Biomedical Research Center, Health Sciences Technology Park, University of Granada, 18016 Granada, Spain  \n3 Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, Campus de Cartuja s/n, 18071 Granada, Spain  \n4 Instituto de Investigación Biosanitaria IBS.GRANADA, Complejo Hospitalario Universitario de Granada, 18014 Granada, Spain  \n5 Children’s Hospital of Eastern Ontario Research Institute, Ottawa, ON K1H 8L1, Canada  \n* Correspondence: jrplaza@ugr.es; Tel.: +34-958241000 (ext. 41599)† These authors contributed equally to this work.  \nAbstract: Breast cancer represents the most prevalent form of cancer and the leading cause of cancer-related mortality among females worldwide. It has been reported that several risk factors contribute to the appearance and progression of this disease. Despite the advancements in breast cancer treatment, a significant portion of patients with distant metastases still experiences no cure. The extracellular matrix represents a potential target for enhanced serum biomarkers in breast cancer. Furthermore, extracellular matrix degradation and epithelial–mesenchymal transition constitute the primary stages of local invasion during tumorigenesis. Additionally, the microbiome has a potential influence on diverse physiological processes. It is emerging that microbial dysbiosis is a significant element in the development and progression of various cancers, including breast cancer. Thus, a better understanding of extracellular matrix and microbiome interactions could provide novel alternatives to breast cancer treatment and management. In this review, we summarize the current evidence regarding the intricate relationship between breast cancer with the extracellular matrix and the microbiome. We discuss the arising associations and future perspectives in this field.  \nKeywords: breast cancer; extracellular matrix; microbiome; tumorigenesis  \n1. Introduction  \nBreast cancer (BC) is a severe, life-threatening condition widely recognized as a prevalent contributor to cancer mortality, being the most prevalent malignancy afflicting women [1] . Despite significant advancements in its diagnosis and treatment, BC metastasis continues to be a leading cause of mortality among women, causing an imperative need for a deeper understanding of the molecular and cellular mechanisms that empower cancer cells to not only survive but also expand [2] . Several risk factors have been described in the appearance and progression of this disease, including genetic factors (such as inherited mutations in genes), reproductive factors (e.g., age at menarche or age at first live birth), high breast density, dietary patterns, alcohol consumption, sedentary lifestyle, or obesity [3–5] . In this complex scenario, preclinical and clinical data have accumulated evidence indicating that some of these risk factors may ","cbCaim0K6lUY4k3F","https://ap.wps.com/l/cbCaim0K6lUY4k3F","pdf",1416006,16,"English","# Introduction\n## Risk factors and mechanisms\n## Conventional treatments and unmet needs\n## Microbiome involvement and microenvironments\n## ECM turnover and biomarker potential","[{\"question\":\"What makes breast cancer particularly deadly despite treatment advances?\",\"answer\":\"Breast cancer remains the most prevalent cancer and a leading cause of cancer-related mortality among women. Metastasis continues to drive death, and distant metastases still often lack cure.\"},{\"question\":\"How does the extracellular matrix contribute to local invasion in breast cancer?\",\"answer\":\"Extracellular matrix degradation and epithelial–mesenchymal transition represent primary stages of local invasion during tumor development. ECM homeostasis and turnover are also linked to biomarker potential.\"},{\"question\":\"What role can the microbiome play in breast cancer development and progression?\",\"answer\":\"Microbial dysbiosis is described as a significant element in the development and progression of cancers, including breast cancer. The microbiome can influence multiple physiological pathways and can alter initiation, proliferation, genetic instability, or apoptosis.\"}]","Breast Cancer: Extracellular Matrix and Microbiome Interactions - A Review | PDF",1789997449]