title: CNS metastases in breast cancer: old challenge, new frontiers.
abstract: Despite major therapeutic advances in the management of patients with breast cancer, central nervous system (CNS) metastases remain an intractable problem, particularly in patients with metastatic HER2-positive and triple-negative breast cancer. As systemic therapies to treat extracranial disease improve, some patients are surviving longer, and the frequency of CNS involvement seems to be increasing. Furthermore, in the early-stage setting, the CNS remains a potential sanctuary site for relapse. This review highlights advances in the development of biologically relevant preclinical models, including the development of brain-tropic cell lines for testing of agents to prevent and treat brain metastases, and summarizes our current understanding of the biology of CNS relapse. From a clinical perspective, a variety of therapeutic approaches are discussed, including methods to improve drug delivery, novel cytotoxic agents, and targeted therapies. Challenges in current trial design and endpoints are reviewed. Finally, we discuss promising new directions, including novel trial designs, correlative imaging techniques, and enhanced translational opportunities.
authors.affiliation: Authors' Affiliations: Dana-Farber Cancer Institute, Boston, Massachusetts; Medical Oncology Branch, Center for Cancer Research, National Cancer Institute; Women's Cancers Section, Laboratory of Molecular Pharmacology; and Biostatistics and Data Management Section, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
authors.forename: Nancy U
authors.initials: NU
authors.lastname: Lin
authors.forename: Laleh
authors.initials: L
authors.lastname: Amiri-Kordestani
authors.forename: Diane
authors.initials: D
authors.lastname: Palmieri
authors.forename: David J
authors.initials: DJ
authors.lastname: Liewehr
authors.forename: Patricia S
authors.initials: PS
authors.lastname: Steeg
mesh_terms: D020533:Angiogenesis Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology* / Q000628:therapy; D016543:Central Nervous System Neoplasms / Q000000981:diagnostic imaging / Q000556:secondary* / Q000628:therapy; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D009364:Neoplasm Recurrence, Local / Q000556:secondary* / Q000628:therapy; D017239:Paclitaxel / Q000493:pharmacokinetics / Q000627:therapeutic use; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D000068878:Trastuzumab
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000972:Antineoplastic Agents, Phytogenic; D019275:Radiopharmaceuticals; D000068878:Trastuzumab; D017239:Paclitaxel