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The fibroblastic reticular cell (FRC) network within ALNs provides structural support and mediates immune homeostasis, but we have yet to elucidate whether this network changes during BC progression. An unbiased computational approach was used to quantify features of the immunolabelled FRC network in ALNs derived from patients with BC. Platelet\u2010derived growth factor receptor \u03b2 (PDGFR\u03b2) was identified as a robust immunomarker for human FRC and used to quantify how FRC network topology changes during BC progression and after treatment. Formalin\u2010fixed paraffin\u2010embedded ALNs (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009331) from 179\u2009patients with BC and 23 benign reactive controls were assessed for FRC network metrics, including lacunarity and branchpoints, alongside de\u2010identified clinico\u2010pathological data. These data were then integrated using multivariate, principal component and survival analyses. In node\u2010negative, post\u2010neoadjuvant chemotherapy triple\u2010negative BC, denser FRC networks in uninvolved nodes significantly improved survival (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0365). [Correction added on 09 May 2026, after first online publication: The word \u2018treatment\u2010na\u00efve\u2019 has been corrected to \u2018post\u2010neoadjuvant chemotherapy\u2019 in the preceding sentence.] Conversely, similar changes seen in node\u2010positive BC significantly worsened survival (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0407), regardless of BC subtype or treatment. In metastatic ALNs, FRC network disruption grew proportionately to axillary tumour burden, and this significantly correlated with poorer outcomes (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.043). Interestingly, increased FRC alignment within these metastases significantly improved survival (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0205). This study showed that changes in human ALN FRC network topology predicts BC prognosis. This could improve how we risk stratify patients in future, and provide a new avenue for mechanistic, translational research. \u00a9 2026 The Author(s).\n                    <jats:italic>The Journal of Pathology<\/jats:italic>\n                    published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.70065","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T09:47:54Z","timestamp":1776678474000},"page":"348-362","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Topological analysis of the human lymph node reticular network predicts outcome in breast cancer"],"prefix":"10.1002","volume":"269","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-7023-1399","authenticated-orcid":false,"given":"Amy M","family":"Llewellyn","sequence":"first","affiliation":[{"name":"Translational 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