{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T04:28:46Z","timestamp":1786422526532,"version":"build-2736575974"},"reference-count":147,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2020,11,12]],"date-time":"2020-11-12T00:00:00Z","timestamp":1605139200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The management of breast cancer (BC) has rapidly evolved in the last 20 years. The improvement of systemic therapy allows a remarkable control of extracranial disease. However, brain (BM) and leptomeningeal metastases (LM) are frequent complications of advanced BC and represent a challenging issue for clinicians. Some prognostic scales designed for metastatic BC have been employed to select fit patients for adequate therapy and enrollment in clinical trials. Different systemic drugs, such as targeted therapies with either monoclonal antibodies or small tyrosine kinase molecules, or modified chemotherapeutic agents are under investigation. Major aims are to improve the penetration of active drugs through the blood\u2013brain barrier (BBB) or brain\u2013tumor barrier (BTB), and establish the best sequence and timing of radiotherapy and systemic therapy to avoid neurocognitive impairment. Moreover, pharmacologic prevention is a new concept driven by the efficacy of targeted agents on macrometastases from specific molecular subgroups. This review aims to provide an overview of the clinical and molecular factors involved in the selection of patients for local and\/or systemic therapy, as well as the results of clinical trials on advanced BC. Moreover, insight on promising therapeutic options and potential directions of future therapeutic targets against BBB and microenvironment are discussed.<\/jats:p>","DOI":"10.3390\/ijms21228534","type":"journal-article","created":{"date-parts":[[2020,11,12]],"date-time":"2020-11-12T10:00:32Z","timestamp":1605175232000},"page":"8534","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Management of Brain and Leptomeningeal Metastases from Breast Cancer"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3243-0059","authenticated-orcid":false,"given":"Alessia","family":"Pellerino","sequence":"first","affiliation":[{"name":"Department of Neuro-Oncology, University and City of Health and Science Hospital, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2198-1480","authenticated-orcid":false,"given":"Valeria","family":"Intern\u00f2","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Human Oncology, University of Bari Aldo Moro, 70121 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Mo","sequence":"additional","affiliation":[{"name":"Department of Neuro-Oncology, University and City of Health and Science Hospital, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Franchino","sequence":"additional","affiliation":[{"name":"Department of Neuro-Oncology, University and City of Health and Science Hospital, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Soffietti","sequence":"additional","affiliation":[{"name":"Department of Neuro-Oncology, University and City of Health and Science Hospital, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Rud\u00e0","sequence":"additional","affiliation":[{"name":"Department of Neuro-Oncology, University and City of Health and Science Hospital, 10126 Turin, Italy"},{"name":"Department of Neurology, Castelfranco Veneto and Treviso Hospital, 31100 Treviso, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,12]]},"reference":[{"key":"ref_1","first-page":"4655","article-title":"Recent trends in epidemiology of brain metastases: An overview","volume":"32","author":"Tabouret","year":"2012","journal-title":"Anticancer Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.critrevonc.2019.01.020","article-title":"Leptomeningeal carcinomatosis in patients with breast cancer","volume":"135","author":"Franzoi","year":"2019","journal-title":"Crit. 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