Brain metastasis-free survival in patients with HER2-positive metastatic breast cancer.

Abstract

41 Background: Brain metastases (BM) are diagnosed in up to 40% of patients with HER2-positive metastatic breast cancer (MBC). Since the introduction of trastuzumab in 1999, a rising incidence of BM was reported. We aimed to identify factors that prolong BM free survival (BMFS) in all HER2-positive patients (pts) treated for MBC at the Medical University of Vienna from 1999-2009. Methods: BMFS was defined as primary study endpoint and measured as the interval from diagnosis of metastatic disease until diagnosis of brain metastases. 201 pts with HER2-positive MBC were identified from a breast cancer database. 82 pts (40.8%) were diagnosed with BM; 13 pts were excluded from this analysis as brain was the first site of disease progression. Complete data sets of 69 pts with pathologically verified HER2-positive MBC were available. HER2 status was analyzed by immunohistochemistry and reanalyzed by FISH if a score of 2= was gained. BMFS was estimated by using the Kaplan-Meier product-limit method; factors significantly associated with BMFS in the univariate analysis were included into a Cox proportional hazard model. Results: Median BMFS was 25 months (m; 95%CI 13.37-36.63 m). Trastuzumab-based treatment significantly prolonged median BMFS (29 vs. 11 m; p<0.01); BMFS was further improved by trastuzumab treatment in multiple lines (30 vs. 17 m; p=0.045). Co-positivity for estrogen receptor (ER) and HER2 predicted for longer BMFS (30 vs. 15 m; p<0.05). Further variables such as prior exposure to capecitabine, presence of visceral metastasis, presence of lung metastasis, stage IV disease at primary diagnosis, as well as disease free interval from adjuvant therapy were not significantly associated with BMFS. In the Cox regression model, positive ER status (HR 2.03; 95%CI 1.22-3.36; p<0.05) and trastuzumab-based treatment (HR 2.72; 95%CI 1.20-6.17; p=0.017) remained independent predictors for longer BMFS. Conclusions: Trastuzumab-based therapy significantly prolongs BMFS in HER2-positive pts with MBC, probably due to improved systemic disease control. In line with known better survival outcome, ER/HER2 co-positive disease appears to be a less aggressive subtype of HER2-positive breast cancer associated with longer BMFS.