Annals of Oncology Advance Access published online on March 11, 2008
Annals of Oncology, doi:10.1093/annonc/mdn036
Defining prognosis for women with breast cancer and CNS metastases by HER2 status
1 Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
2 Department of Medical Oncology, Dubai Hospital, UAE
3 Department of Quantitative Sciences
4 Department of Pathology and
5 Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
* Correspondence to: Dr S. Dawood, Department of Medical Oncology, Dubai Hospital, UAE. Tel: 832-677-3432; Fax: 8572770918; E-mail: shaheenah_d{at}yahoo.com
Background: The purpose of this retrospective study was to determine, in a cohort of patients with breast cancer and central nervous system (CNS) metastases, the effect of trastuzumab in patients with human epidermal growth factor receptor 2 (HER2)-positive disease and to compare this with that of patients with HER2-negative disease.
Methods: Five hundred and ninety-eight patients with invasive breast cancer, CNS metastases and known HER2 status were identified. Time to CNS metastases and survival after CNS metastases were estimated by the Kaplan–Meier method, and Cox models were fitted to determine the association between HER2 status, trastuzumab treatment and outcomes after adjustment for other patient characteristics.
Results: In the multivariable model, patients with HER2-negative disease [Hazard ratio (HR) 1.50, 95% confidence interval (CI) 1.15–1.95, P = 0.003] and patients with HER2-positive disease who did not receive trastuzumab (HR 2.13, 95% CI 1.51–3.00, P < 0.0001) had shorter times to CNS metastases compared with patients with HER2-positive disease who had received trastuzumab as first-line therapy for metastases. Furthermore, patients with HER2-negative disease (HR 1.66, 95% CI 1.31–2.12, P < 0.0001) and patients with HER2-positive disease who had never received trastuzumab (HR 1.34, 95% CI 0.78–2.30, P = 0.28) had an increased hazard of death compared with patients with HER2-positive disease who had received trastuzumab before or at the time of CNS metastases diagnosis.
Conclusion: In our cohort of patients with breast cancer and CNS metastases, patients with HER2-positive disease treated with trastuzumab had longer times to development of and better survival from CNS metastases compared with patients with HER2-positive disease who had never received trastuzumab and patients with HER2-negative breast cancer.
brain metastases, breast cancer, HER2, trastuzumab
Received for publication September 9, 2007. Revision received January 22, 2008. Accepted for publication January 24, 2008.