Complete radiologic response and long-term survival with use of systemic high-dose methotrexate for breast cancer-associated leptomeningeal disease

Cesar A. Santa-Maria, Ashley Cimino-Mathews, Kendall F. Moseley, Antonio C. Wolff, Jaishri O. Blakeley, Roisin M. Connolly*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Breast cancer is one of the most common malignancies that metastasizes to the leptomeninges, with human epidermal growth factor receptor 2 (HER2)- tumors having a higher incidence of central nervous system involvement than other breast cancer subtypes. Conventional treatment for leptomeningeal disease includes radiation therapy and intrathecal chemotherapy, the latter requiring an invasive procedure for administration, with the potential for significant adverse effects. Despite standard treatment approaches, patients with leptomeningeal disease usually have a poor prognosis, with a median survival of -6 months. Highdose methotrexate is one of the few chemotherapeutic agents known to cross the blood-brain barrier; however, data are limited as to its clinical efficacy. We present the case of a patient with advanced HER2- breast cancer who developed new onset headaches and disequilibrium secondary to both intracerebral and leptomeningeal disease. Treatment with high-dose systemic methotrexate concurrent with trastuzumab resulted in resolution of her symptoms as well as a longlasting clinical and radiologic remission that exceeded that expected with conventional therapies. Prospective studies that evaluate the role of agents that penetrate the blood-brain barrier, including highdose methotrexate, are clearly warranted in patients with leptomeningeal disease. In addition, this patient population should ideally be managed in a center with personnel experienced in treating this rare manifestation of malignancy in a multidisciplinary fashion.

Original languageEnglish (US)
Pages (from-to)445-449
Number of pages5
JournalClinical Breast Cancer
Volume12
Issue number6
DOIs
StatePublished - Dec 1 2012

Keywords

  • Blood brain barrier
  • HER2 positive breast cancer
  • High-dose methotrexate
  • Leptomeningeal disease
  • Metastatic breast cancer

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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