{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T14:24:46Z","timestamp":1777386286139,"version":"3.51.4"},"reference-count":151,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,4,8]],"date-time":"2022-04-08T00:00:00Z","timestamp":1649376000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["EXPL\/BIA-BQM\/0255\/2021"],"award-info":[{"award-number":["EXPL\/BIA-BQM\/0255\/2021"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Breast cancer (BRCA) remains as one the most prevalent cancers diagnosed in industrialised countries. Although the overall survival rate is high, the dissemination of BRCA cells to distant organs correlates with a significantly poor prognosis. This is due to the fact that there are no efficient therapeutic strategies designed to overcome the progression of the metastasis. Over the past decade, critical associations between stress and the prevalence of BRCA metastases were uncovered. Chronic stress and the concomitant sympathetic hyperactivation have been shown to accelerate the progression of the disease and the metastases incidence, specifically to the bone. In this review, we provide a summary of the sympathetic profile on BRCA. Additionally, the current knowledge regarding the sympathetic hyperactivity, and the underlying adrenergic signalling pathways, involved on the development of BRCA metastasis to distant organs (i.e., bone, lung, liver and brain) will be revealed. Since bone is a preferential target site for BRCA metastases, greater emphasis will be given to the contribution of \u03b12- and \u03b2-adrenergic signalling in BRCA bone tropism and the occurrence of osteolytic lesions.<\/jats:p>","DOI":"10.3390\/cancers14081881","type":"journal-article","created":{"date-parts":[[2022,4,8]],"date-time":"2022-04-08T12:11:14Z","timestamp":1649419874000},"page":"1881","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Stress in Metastatic Breast Cancer: To the Bone and Beyond"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0644-0202","authenticated-orcid":false,"given":"Catarina","family":"Louren\u00e7o","sequence":"first","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (I3S), Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"INEB\u2014Instituto Nacional de Engenharia Biom\u00e9dica, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Cancer Biology and Epigenetics Group, Research Center of IPO Porto (CI-IPOP)\/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)\/Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4587-2470","authenticated-orcid":false,"given":"Francisco","family":"Concei\u00e7\u00e3o","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (I3S), Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"INEB\u2014Instituto Nacional de Engenharia Biom\u00e9dica, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"ICBAS-UP\u2014School of Medicine & Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4186-5345","authenticated-orcid":false,"given":"Carmen","family":"Jer\u00f3nimo","sequence":"additional","affiliation":[{"name":"Cancer Biology and Epigenetics Group, Research Center of IPO Porto (CI-IPOP)\/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)\/Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, Portugal"},{"name":"Department of Pathology and Molecular Immunology\u2014ICBAS-UP, 4050-313 Porto, Portugal"}]},{"given":"Meriem","family":"Lamghari","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (I3S), Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"INEB\u2014Instituto Nacional de Engenharia Biom\u00e9dica, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"ICBAS-UP\u2014School of Medicine & Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8498-0664","authenticated-orcid":false,"given":"Daniela M.","family":"Sousa","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (I3S), Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"INEB\u2014Instituto Nacional de Engenharia Biom\u00e9dica, Universidade do Porto, 4200-135 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,8]]},"reference":[{"key":"ref_1","unstructured":"Ferlay, J.E.M., Lam, F., Colombet, M., Mery, L., Pi\u00f1eros, M., Znaor, A., Soerjomataram, I., and Bray, F. 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