Trastuzumab (T) and CNS metastases in women with HER-2 positive metastatic breast cancer (MBC)

Abstract

683 Background: A high rate of CNS metastases has been described in women with MBC over-expressing HER-2 who receive T-based therapy. The aim of this study was to examine the frequency of and potential risk factors for CNS metastases in these women. Our a priori hypotheses were that in MBC patients treated with T, CNS metastases occurred: 1) more frequently than historical controls, and 2) in women with controlled systemic disease. Methods: A retrospective cohort study of 28 patients with MBC cancer over-expressing HER-2 and treated with T and chemotherapy was performed. Results: 22/25 (88%) patients who initially responded to T had progressed by the time of analysis. CNS metastases occurred in 11/28 (39%) patients and the remaining 11 patients had progressed elsewhere. At diagnosis of CNS metastases, 9/11 (82%) patients had controlled systemic disease (CR=2, PR=6, SD=1, PD=2 patients). There were trends for patients with CNS metastases to have > 1 site of metastatic disease at the commencement of T therapy (P=0.06), and to be hormone receptor negative at initial diagnosis (P=0.14). The median time to diagnosis of CNS metastases after the commencement of T therapy was 30.8 months (range 16–49). The median survival after diagnosis of CNS metastases was 30.6 months (range 4–75). Conclusions: Historically, CNS metastases have been reported to occur in 10–16% of women with MBC, with a median survival of < 1 year. This study demonstrates a significantly higher rate of CNS metastases (39%) in HER-2 positive MBC patients treated with T. At CNS metastases most patients had controlled systemic disease and the median survival after CNS relapse was over 2 years. We suggest aggressive management of CNS disease in this population. Additional strategies to decrease the incidence of CNS metastases in these patients may include prophylactic whole brain irradiation and the development of novel pharmacological agents with successful CNS penetration. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Australian New Zealand Breast Cancer Trials Group, Genentech, Roche Roche