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Complete response in HER2+ leptomeningeal carcinomatosis from breast cancer with intrathecal trastuzumab
Mafalda Oliveira • Sofia Braga • Jose ́ Lu ́ıs Passos-Coelho • Ricardo Fonseca • Joa ̃o Oliveira
Received: 15 February 2011 / Accepted: 16 February 2011 / Published online: 3 March 2011 Ó Springer Science+Business Media, LLC. 2011
M. Oliveira (&) J. L. Passos-Coelho J. Oliveira Medical Oncology Department, Instituto Portugueˆs de Oncologia de Lisboa Francisco Gentil, Rua Professor Lima Basto, 1099-023 Lisbon, Portugal e-mail:
mafalda.moliveira@gmail.com
S. Braga Instituto Gulbenkian de Cieˆncia, Rua da Quinta Grande, 6, P-2780-156 Oeiras, Portugal
R. Fonseca Pathology Department, Instituto Portugueˆs de Oncologia de Lisboa Francisco Gentil, Rua Professor Lima Basto, 1099-023 Lisbon, Portuga
BRIEF REPORT
Abstract
Introduction
Leptomeningeal carcinomatosis (LC) is a rare but rapidly fatal event in the natural history of breast cancer [1]. HER2? breast cancer has an increased risk of central nervous system (CNS) metastases [2] but there are little data on LC frequency in these tumors [3]. Trastuzumab, a monoclonal antibody against the extracellular domain of the HER2 receptor, is highly effective in systemic control of HER2? metastatic breast cancer [4] but it is not clear if it can penetrate the intact blood brain barrier (BBB) [5]. We report the case of a patient who received weekly intrathecal (IT) trastuzumab for LC from HER2? breast cancer for 18 months, with impressive neurological benefit.
Case report
A 40 year-old woman presented in April 2003 with a left- sided cT4bN1M0 estrogen receptor (ER) positive (70% of cells) invasive ductal carcinoma. She received six cycles of neoadjuvant chemotherapy (5-FU 500 mg/m2, epirubicin 100 mg/m. Trastuzumab, a monoclonal antibody against the HER2 receptor, is a major breakthrough in the treat- ment of HER2? breast cancer. However, its high molec- ular weight precludes it from crossing the intact blood– brain barrier, making the central nervous system a sanc- tuary to HER2? breast cancer metastases. We prospec- tively assessed functional outcome and toxicity of administering trastuzumab directly into the cerebrospinal fluid of a patient with leptomeningeal carcinomatosis (LC) and brain metastases from HER2? breast cancer that had already been treated with other intrathecal chemotherapy, with no benefit. Upon signed informed consent, weekly lumbar puncture with administration of trastuzumab 25 mg was begun to a 44 year-old women with metastatic breast cancer (lymph node, bone, lung, and liver involvement) previously treated with tamoxifen, letrozole, anthracy- clines, taxanes, capecitabine, intravenous trastuzumab, and lapatinib. She received 67 weekly administrations of intrathecal trastuzumab with marked clinical improvement and no adverse events. She survived 27 months after LC diagnosis. A complete leptomeningeal response, with no
evidence of leptomeningeal metastasis at necropsy, was achieved. We believe that intrathecal trastuzumab admin- istration should be prospectively evaluated to confirm clinical activity and optimize dose, schedule, and duration of treatment.
Keywords Intrathecal trastuzumab Leptomeningeal carcinomatosis HER2? breast cancer