New target therapies for brain metastases from breast cancer

G. Metro, A. Fabi

Research output: Contribution to journalArticlepeer-review

Abstract

Central nervous system (CNS) metastases from breast cancer (BC) represent an important cause of disease-related morbidity and mortality. For BC patients who develop CNS metastases, local control measures (both surgery and radiation) are essentially palliative and usually poorly effective, with systemic therapies often failing to achieve optimal control mainly due to the presence of the blood-brain barrier which hampers adequate penetration of therapeutic agents into the brain. However, recent evidence suggests that the status of the human epidermal growth factor receptor-2 (HER2) strongly influences the incidence of CNS metastases and the survival of BC patients from the time of development of CNS metastases, with HER2-positive (HER2+) patients generally experiencing higher rates of CNS metastases and prolonged overall survival compared to patients with HER2-negative disease. This phenomenon likely reflects the difficult CNS drug-penetration and improved control of extra-CNS disease following the clinical use of the anti-HER2 monoclonal antibody trastuzumab. Importantly, this HER2-based survival difference has important implications when planning the optimal treatment of BC patients with CNS metastases. To date, although no systemic therapy has been specifically approved for the treatment of CNS metastases from BC, several targeted agents are being clinically developed for this purpose. In the present review we will discuss the targeted therapies that are under investigation for the treatment of CNS metastases from BC, highlighting the different implications based on whether a given agent is being developed to target CNS metastases from HER2+ or HER2-negative breast cancer.

Original languageEnglish
Pages (from-to)210-217
Number of pages8
JournalCurrent Cancer Drug Targets
Volume12
Issue number3
Publication statusPublished - Mar 2012

Keywords

  • Blood-brain barrier
  • Brain metastases
  • Breast cancer
  • Central nervous system
  • HER2
  • Lapatinib
  • Trastuzumab
  • Triple negative

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Cancer Research

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