{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T15:11:27Z","timestamp":1791645087054,"version":"4.3.4"},"reference-count":24,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2003,5,29]],"date-time":"2003-05-29T00:00:00Z","timestamp":1054166400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2003,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>Women with HER\u20102 overexpressing metastatic breast carcinoma benefit from trastuzumab\u2010based therapy, but trastuzumab does not cross the blood\u2010brain barrier. The authors characterized central nervous system (CNS) disease in these women.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Using pharmacy records, the authors retrospectively identified 153 women treated with trastuzumab alone or with chemotherapy for HER\u20102\u2013positive metastatic breast carcinoma at Dana\u2010Farber Partners Cancer Care from June 1998 to December 2000. A study cohort of 122 patients was identified after excluding patients without adequate clinical follow\u2010up or who had CNS disease before trastuzumab treatment. Central nervous system disease was defined as one or more brain metastases or as leptomeningeal carcinomatosis. The median follow\u2010up of this cohort was 23 months.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Central nervous system metastases were identified in 34% of patients (95% confidence interval, 26\u201344%) at a median of 16 months after diagnosis of metastatic breast carcinoma and 6 months from the beginning of trastuzumab therapy. Ninety\u2010three percent of patients with CNS disease presented with clinical symptoms. Five percent of patients with CNS disease had leptomeningeal involvement alone, although 14% had leptomeningeal involvement and parenchymal brain metastases. Fifty percent of patients were responding or had stable disease while receiving trastuzumab at other disease sites at the time of diagnosis of CNS metastasis. The median survival period after CNS metastases was 13 months. Fifty percent of patients died of progressive CNS disease. Patients receiving trastuzumab as first\u2010line therapy for metastatic disease frequently developed brain metastases while responding to or stable on trastuzumab at other disease sites.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>Metastatic breast carcinoma to the CNS is common among patients receiving trastuzumab\u2010based therapy, including patients responding to therapy outside the CNS. This may be due either to predilection for the CNS by HER\u20102\u2013positive tumor cells and\/or poor penetration of the CNS by trastuzumab or to improved visceral disease control leading to a longer life and onset of late tumor spread to the CNS. Efforts to characterize other risk factors for development of CNS disease, optimal screening algorithms, and new treatment strategies may be warranted. Cancer 2003;97:2972\u20137. \u00a9 2003 American Cancer Society.<\/jats:p>\n                    <jats:p>DOI 10.1002\/cncr.11436<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cncr.11436","type":"journal-article","created":{"date-parts":[[2003,5,30]],"date-time":"2003-05-30T06:05:14Z","timestamp":1054274714000},"page":"2972-2977","source":"Crossref","is-referenced-by-count":632,"title":["Central nervous system metastases in women who receive trastuzumab\u2010based therapy for metastatic breast carcinoma"],"prefix":"10.1002","volume":"97","author":[{"given":"Johanna C.","family":"Bendell","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan M.","family":"Domchek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harold 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