Application of intrathecal trastuzumab for treatment of meningeal carcinomatosis in HER2-overexpressing metastatic breast cancer

BACKGROUND: When the humanized anti-HER2 monoclonal antibody trastuzumab is given intravenously, very little reaches the cerebrospinal fluid (CSF). Thus, carcinomatous meningitis may occur in patients with complete systemic remission induced by trastuzumab therapy. Intracerebral injections in rats with meningeal carcinomatosis have shown an increase in survival without clinical or histologic toxic effects. Three cases of meningeal dissemination from breast cancer treated with intrathecally administered trastuzumab have been reported clinically without any significant adverse events. Here we report a case of a 66-year-old woman with HER2-overexpressing metastatic breast cancer who suffered from meningeal carcinomatosis and was treated with intrathecal trastuzumab. RESULTS: The patient developed invasive apocrine carcinomas (six involved nodes, hormone receptor-negative and HER2 3+) in her right breast and was initially treated with mastectomy and axillary nodal dissection followed by chemotherapy (CEF; cyclophosphamide, doxorubicine, and 5-fluorouracil followed by docetaxel) and radiotherapy (50 Gy). Two years later, the patient had episodes of vertigo and headaches. MRI and CSF analysis indicated brain metastasis and meningeal carcinomatosis without any metastatic lesions other than these metastatic sites. An Ommaya reservoir for intrathecal treatment with methotrexate and cytarabine was placed surgically, and the patient was treated with intrathecal chemotherapy and whole-brain radiotherapy (40Gy). Meningeal enhancement and brain tumor on MRI and tumor cell counts in CSF still remained after the maximal treatment cycle. As the next choice of treatment, intrathecal therapy with weekly trastuzumab (25 mg/body) was begun after approval of IRB. After 6 injections of trastuzumab, malignant cells in CSF disappeared and interestingly the brain tumor shrank. The patient still continues intrathecal trastuzumab without any clinical toxic effects. CONCLUSIONS: Considering the few options for treatment of meningeal dissemination in MBC, this approach might be a viable method of treatment for meningeal dissemination of HER2-positive MBC patients through appropriate clinical trials.