Abstract 2276: Serum endoglin and uPA change predicts PFS and overall survival in first line trastuzumab-treated breast cancer

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Background: About half of HER2-positive breast cancer patients will respond to first-line trastuzumab-containing therapy, but of these most will progress within a year with acquired resistance. Since trastuzumab treatment is now used in the HER2-positive adjuvant breast cancer setting, trastuzumab resistance will continue to be a recurring clinical problem, and better predictive and prognostic biomarkers are urgently needed. Methods: Serum TIMP-1, uPA, carbonic anhydrase 9 (CA9), and endoglin (co-receptor for TGF- β) were measured using ELISA in 60 metastatic breast cancer patients before starting first-line trastuzumab-containing therapy, and at the closest 1 month post-trastuzumab blood draw. The TIMP-1, uPA and CA9 ELISAs were from Oncogene Science/Siemens Healthcare Diagnostics, and the endoglin ELISA was from R&D Systems. Progression-free (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and Cox modeling. Results: When serum biomarker change (pretreatment to 1 month post-trastuzumab treatment) was analyzed on a continuous basis, change in serum TIMP-1 and CA 9 were not significant for PFS or OS. However the change in serum endoglin (HR = 1.017, p = 0.013) and serum uPA (HR 1.018, p = 0.006) were significant predictive factors for PFS to first-line trastuzumab treatment. The change in serum endoglin (HR = 1.021, p = 0.004) and serum uPA (HR 1.016, p = 0.03) were also significant prognostic factors for OS: declining serum endoglin or uPA predicted for increased PFS and OS. Changes in serum endoglin and uPA were positively correlated (r = 0.7, p <0.0001). Due to the significant correlation between the change in serum endoglin and uPA levels, these 2 serum biomarkers were analyzed separately along with the change in serum TIMP-1 and CA9 in multivariate analysis. In these analyses, only the change in serum endoglin or uPA was significant. Conclusions: The change in serum endoglin and uPA level from pretreatment to 1 month post-trastuzumab treatment predicted PFS and overall survival in metastatic breast cancer patients treated with first-line trastuzumab-containing therapy. Endoglin (CD105) is a co-receptor for TGF-β, is expressed by human vascular endothelial cells, and plays a major role in angiogenesis. These angiogenesis-related serum biomarkers deserve further study in larger trials of HER2-targeted breast cancer treatment. Supported by a grant from Komen for the Cure. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2276. doi:10.1158/1538-7445.AM2011-2276