title: Sanctuary site leptomeningeal metastases in HER-2 positive breast cancer: A review in the era of trastuzumab.
abstract: The development of trastuzumab and other targeted systemic therapies has transformed the management of HER-2 positive breast cancers. However, as patients live longer and systemic therapies may not cross the blood brain barrier a rising number of patients are developing leptomeningeal metastases and brain metastases as a sanctuary site of disease. Intrathecal trastuzumab has been reported to treat these. We describe a breast cancer patient with HER-2 positive leptomeningeal disease in the spinal cord successfully treated with intrathecal trastuzumab and methotrexate, alongside systemic anti-HER-2 therapy and radiotherapy. We also review the literature to date on the efficacy and safety of intrathecal trastuzumab, and recent evidence suggesting that intrathecal trastuzumab passes via the blood brain barrier into the serum to achieve intravenous concentrations similar to that seen with systemic therapy alone. Overall, intrathecal trastuzumab appears to be a safe and often effective treatment for leptomeningeal metastases in HER-2 positive breast cancer. Ongoing phase I and II studies are required to determine optimum dosing schedules, validate CSF and CSF-to-serum pharmacokinetics, determine efficacy, and to assess the added benefits or disadvantages of prior radiotherapy and concomitant systemic therapy.
authors.affiliation: The Royal Marsden, London, UK. Electronic address: tianakordbacheh@nhs.net.
authors.forename: T
authors.initials: T
authors.lastname: Kordbacheh
authors.affiliation: The Royal Marsden, London, UK.
authors.forename: W Y
authors.initials: WY
authors.lastname: Law
authors.affiliation: The Royal Marsden, London, UK.
authors.forename: I E
authors.initials: IE
authors.lastname: Smith
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy / Q000473:pathology*; D005260:Female; D006801:Humans; D007278:Injections, Spinal; D008577:Meningeal Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000037:antagonists & inhibitors; D013120:Spinal Cord Neoplasms / Q000188:drug therapy* / Q000556:secondary; D000068878:Trastuzumab / Q000008:administration & dosage*
chemical_list: D000970:Antineoplastic Agents; D008727:Methotrexate; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
keywords: HER-2 positive; Intrathecal trastuzumab (Herceptin); Leptomeningeal metastases; Metastatic breast cancer