Originally published as JCO Early Release 10.1200/JCO.2008.19.8481 on September 21 2009

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Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer and Central Nervous System Metastases

From the Emory Winship Cancer Institute, Emory University, GA.

Corresponding author: Brian Leyland-Jones, MD, PhD, Winship Cancer Institute, Emory University School of Medicine, 1365-C, Clifton Rd, #4014i, Atlanta, GA, 30322; e-mail: leyland{at}emory.edu.

Purpose To determine the incidence, outcomes, and current strategies for management of brain metastases in patients with human epidermal growth factor receptor 2 (HER2)–positive breast cancer.

Methods A literature review was performed to obtain data on central nervous system metastases in patients with breast cancer.

Results HER2 amplification/overexpression is a prognostic and predictive factor for the development of CNS metastases. Autopsy data show that the incidence rate for CNS metastases in patients with breast cancer is approximately 30%; this may be higher (ie, 30% to 50%) in patients with HER2-positive disease. Treatment with trastuzumab is not associated with an increased incidence of CNS metastases. Data from three phase III adjuvant trials showed the incidence was similar between patients who received trastuzumab and those who did not. Furthermore, trastuzumab can significantly improve overall survival in HER2-positive patients who already have CNS metastases compared with patients who do not receive trastuzumab or those who have HER2-negative brain metastases. This survival advantage is conferred via systemic control of the disease. The current standard of care for patients with CNS metastases is whole-brain radiotherapy (WBRT), with or without surgery, or stereotactic radiosurgery. In the future, novel therapies or combinations of therapies may additionally improve survival in these patients.

Conclusion The incidence of CNS metastases in trastuzumab-treated patients is similar to that in all patients with HER2-positive disease. Trastuzumab can improve survival in patients with HER2-positive disease with CNS metastases.

Funded in part by Genentech, South San Francisco, CA.

Author's disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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