Central nervous system metastases in women who receive trastuzumab‐based therapy for metastatic breast carcinoma

Cancer - Tập 97 Số 12 - Trang 2972-2977 - 2003
Johanna C. Bendell1, Susan M. Domchek2, Harold J. Burstein3, Lyndsay N. Harris3, Jerry Younger4, Irene Kuter4, Craig A. Bunnell3, Montserrat Rué3, Rebecca Gelman3, Eric P. Winer3
1Department of Adult Oncology, Dana Farber Cancer Institute,Boston Massachusetts 02115, USA.
2Rena Rowan Breast Center, University of Pennsylvania Cancer Center, Philadelphia, Pennsylvania
3Department of Adult Oncology, Dana‐Farber Cancer Institute, Boston, Massachusetts
4Department of Adult Oncology, Massachusetts General Hospital, Boston, Massachusetts

Tóm tắt

AbstractBACKGROUNDWomen with HER‐2 overexpressing metastatic breast carcinoma benefit from trastuzumab‐based therapy, but trastuzumab does not cross the blood‐brain barrier. The authors characterized central nervous system (CNS) disease in these women.METHODSUsing pharmacy records, the authors retrospectively identified 153 women treated with trastuzumab alone or with chemotherapy for HER‐2–positive metastatic breast carcinoma at Dana‐Farber Partners Cancer Care from June 1998 to December 2000. A study cohort of 122 patients was identified after excluding patients without adequate clinical follow‐up 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‐up of this cohort was 23 months.RESULTSCentral nervous system metastases were identified in 34% of patients (95% confidence interval, 26–44%) at a median of 16 months after diagnosis of metastatic breast carcinoma and 6 months from the beginning of trastuzumab therapy. Ninety‐three 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‐line therapy for metastatic disease frequently developed brain metastases while responding to or stable on trastuzumab at other disease sites.CONCLUSIONSMetastatic breast carcinoma to the CNS is common among patients receiving trastuzumab‐based therapy, including patients responding to therapy outside the CNS. This may be due either to predilection for the CNS by HER‐2–positive 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;97:2972–7. © 2003 American Cancer Society.DOI 10.1002/cncr.11436

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Tài liệu tham khảo

10.1038/sj.onc.1201331

10.1126/science.3798106

10.1200/JCO.1996.14.3.737

10.1200/JCO.1999.17.9.2639

10.1200/JCO.1998.16.8.2659

Norton L, 1999, Overall survival (OS) advantage to simultaneous chemotherapy (CRx) plus the humanized anti‐HER2 monoclonal antibody Herceptin (H) in HER2 overexpressing (HER2+) metastatic breast cancer (MBC), Proc Am Soc Clin Oncol., 18, 127a

10.1200/JCO.2001.19.10.2722

10.1200/JCO.2002.07.058

10.1016/S0093-7754(01)90190-3

10.1056/NEJM200103153441101

Takakura K, 1982, Metastatic tumors of the central nervous system

10.1002/1097-0142(197911)44:5<1913::AID-CNCR2820440554>3.0.CO;2-D

10.1002/1097-0142(19831215)52:12<2349::AID-CNCR2820521231>3.0.CO;2-B

10.1002/jso.2930230311

10.1212/WNL.9.2.91

10.1002/1097-0142(19810715)48:2<395::AID-CNCR2820480228>3.0.CO;2-1

Pestalozzi BC, 2000, Trastuzumab in CSF, J Clin Oncol., 11, 2349, 10.1200/JCO.2000.18.11.2349

Lai RK, 2001, The incidence of brain metastases in HER2/neu+ stage IV breast cancer patients, Proc Am Soc Clin Oncol., 666

Miller KD, 2001, Occult central nervous system involvement in patients with metastatic breast cancer: prevalence, predictive factors, and impact on overall survival, Breast Cancer Res Treat., 69, 240a

Wardley AM, 2002, High incidence of brain metastases in patients treated with trastuzumab for metastatic breast cancer at a large cancer center, Proc Am Soc Clin Oncol., 241

Eitzen R, 2002, High incidence of brain metastases (BM) in patients on trastuzumab (H) for advanced breast cancer, Proc Am Soc Clin Oncol., 31

10.1023/A:1006486423827

Maki DD, 2000, Patterns of disease spread in metastatic breast carcinoma: influence of estrogen and progesterone receptor status, AJNR Am J Neuroradiol., 21, 1064

10.1053/srao.2002.35251

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Cancer

Tập 97 Số 12

2972-2977

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