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Cancer Treat Rev. 2018 Jun;67:71-77. doi: 10.1016/j.ctrv.2018.05.004. Epub 2018 May 9.

Tyrosine kinase inhibitors for brain metastases in HER2-positive breast cancer.

Author information

1
Military Institute of Medicine, Department of Oncology, Warsaw, Poland. Electronic address: rdtt@wp.pl.
2
German Breast Group, Neu-Isenburg, Germany; Sana-Klinikum Offenbach, Germany. Electronic address: Sibylle.Loibl@gbg.de.
3
Medical University of Gdańsk, Department of Oncology and Radiotherapy, Gdańsk, Poland. Electronic address: jjassem@gumed.edu.pl.

Abstract

Approximately 30-50% of advanced HER2-positive breast cancer patients will develop central nervous system (CNS) metastases, with an annual risk of around 10%, and a half of them will die from brain progression. An increased risk of brain metastases is also seen in patients with early HER2-positive breast cancer administered curative therapy. Brain metastases in HER2-positive breast cancer patients usually constitute the first site of recurrence. The administration of anti-HER2 monoclonal antibodies, trastuzumab and pertuzumab, considerably delays the onset of symptomatic brain disease: however, the limited penetration of these compounds into the CNS hinders their efficacy. The small-molecule tyrosine kinase inhibitors of epidermal growth factor receptors family have established activity in HER2-positive breast cancer in both advanced disease and neoadjuvant setting. Favorable physico-chemical properties of these compounds allow them for a more efficient penetration through the blood-brain barrier, and hold the promise for more effective prevention and treatment of brain metastases. In this article we review the role of currently available or investigational HER2 tyrosine kinase inhibitors: lapatinib, neratinib, afatinib and tucatinib in the treatment of brain metastases in HER2-positive breast cancer patients.

KEYWORDS:

Afatinib; Breast cancer; Central nervous system (CNS) metastases; HER2; Lapatinib; Neratinib; Small-molecule tyrosine kinase inhibitors; Tucatinib

PMID:
29772459
DOI:
10.1016/j.ctrv.2018.05.004
[Indexed for MEDLINE]

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