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While sentinel lymph nodes are the initial site of metastasis, the molecular mechanisms driving lymphatic spread are still not well understood. Multifarious questions remain on the role, requirement, and significance of the lymphatic system in the context of the distant metastasis of breast cancer. To address these questions, this review explores the recent advancements achieved in studies related to the molecular processes behind lymphatic metastasis in breast cancer, highlighting the tumor microenvironment\u2019s role in supporting circulating tumor cells. We also examine the key molecular pathways involved in metastatic progression by analyzing the cellular, genetic, and physiological factors that drive lymphatic metastasis. The insights gained may contribute to the development of new therapeutic approaches to prevent or mitigate breast cancer metastasis.<\/jats:p>","DOI":"10.3390\/cancers17132134","type":"journal-article","created":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T08:23:22Z","timestamp":1750839802000},"page":"2134","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Molecular Mechanisms of Lymphatic Metastasis in Breast Cancer: An Updated Review"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5774-9600","authenticated-orcid":false,"given":"Fatema","family":"Mahjabeen","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Texas Tech University Health Sciences Center at Amarillo, Amarillo, TX 79106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4359-1301","authenticated-orcid":false,"given":"Samrin F.","family":"Habbani","sequence":"additional","affiliation":[{"name":"Department of Comparative Pathobiology, Purdue University Institute of Cancer Research, Purdue University, West Lafayette, IN 47907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sulma I.","family":"Mohammed","sequence":"additional","affiliation":[{"name":"Department of Small Animal Clinical Sciences and Cancer Control and Population Sciences, University of Florida Health Cancer Center, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1038\/s41591-025-03502-3","article-title":"Global Patterns and Trends in Breast Cancer Incidence and Mortality across 185 Countries","volume":"31","author":"Kim","year":"2025","journal-title":"Nat. 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