{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T01:24:28Z","timestamp":1792718668921,"version":"4.5.0"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,12,6]],"date-time":"2013-12-06T00:00:00Z","timestamp":1386288000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/3.0\/"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2014,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:bold>\n                      There remain no clear guidelines for the optimal management of patients with metastatic breast cancer. To better understand its natural history, we undertook a detailed examination of 197 autopsies performed on women who died of breast cancer. We reviewed clinical, treatment and pathological aspects of all cases and, additionally, pathological features and biomarker expression (\n                      <jats:styled-content style=\"fixed-case\">ER<\/jats:styled-content>\n                      ,\n                      <jats:styled-content style=\"fixed-case\">PgR<\/jats:styled-content>\n                      ,\n                      <jats:styled-content style=\"fixed-case\">HER2<\/jats:styled-content>\n                      ,\n                      <jats:styled-content style=\"fixed-case\">EGFR<\/jats:styled-content>\n                      , p53, Ki67, c\u2010Kit,\n                      <jats:styled-content style=\"fixed-case\">CK AE1<\/jats:styled-content>\n                      \/\n                      <jats:styled-content style=\"fixed-case\">AE3<\/jats:styled-content>\n                      ) were assessed in detail for the primary tumour and matched metastases for 55 of the cases. Genomes of the primary tumour and multiple metastases were analysed by array\u2010based comparative genomic hybridization for six cases\n                      <jats:sup>##<\/jats:sup>\n                      . 945 metastatic deposits were identified, with a median of four\/patient. The most common organs involved were lung\/pleura (80%), bone (74%), liver (71%) and non\u2010axillary lymph nodes (55%). Major findings included: (a) patients with\n                      <jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content>\n                      metastases were more likely to have bone metastases (\n                      <jats:italic>p &lt;<\/jats:italic>\n                      0.013); (b) younger age was associated with metastasis to the liver (\u2264 49\u2009years;\n                      <jats:italic>p &lt;<\/jats:italic>\n                      0.001) and to gynaecological organs (\u2264 49\u2009years;\n                      <jats:italic>p =<\/jats:italic>\n                      0.001); (c) surgical excision of the primary tumour was associated with metastasis to the liver (\n                      <jats:italic>p =<\/jats:italic>\n                      0.002); and (d)\n                      <jats:styled-content style=\"fixed-case\">ER<\/jats:styled-content>\n                      and\n                      <jats:styled-content style=\"fixed-case\">PgR<\/jats:styled-content>\n                      showed down\u2010regulation during progression in a non\u2010random manner, particularly in lung\/pleura (\n                      <jats:styled-content style=\"fixed-case\">ER<\/jats:styled-content>\n                      ;\n                      <jats:italic>p &lt;<\/jats:italic>\n                      0.001), liver and bone metastases. Genomic analysis revealed\n                      <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>\n                      copy number variation between the primary tumour and metastases (\n                      <jats:italic>e.g.<\/jats:italic>\n                      amplification of 2q11.2\u2013q12.1 and 10q22.2\u2013q22.3) but little variation between metastases from the same patient. In summary, the association of\n                      <jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content>\n                      and bone metastases, liver and gynaecological metastases in young women and the risk of liver metastases following surgery have important implications for the management of patients with breast cancer. Clonal heterogeneity of the primary tumour is important in developing metastatic propensity and the change in tumour phenotype during progression\/colonization highlights the importance of sampling metastatic disease for optimal treatment strategies. \u00a9 2013 The Authors.\n                      <jats:italic>Journal of Pathology<\/jats:italic>\n                      published by John Wiley &amp; Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.\n                    <\/jats:bold>\n                  <\/jats:p>","DOI":"10.1002\/path.4288","type":"journal-article","created":{"date-parts":[[2013,10,11]],"date-time":"2013-10-11T22:35:11Z","timestamp":1381530911000},"page":"23-31","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":172,"title":["Metastatic progression of breast cancer: insights from 50\u2009years of autopsies"],"prefix":"10.1002","volume":"232","author":[{"given":"Margaret 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