Elevated plasma endoglin (CD105) predicts decreased response and survival in metastatic breast cancer patients

10091 Background: Endoglin (CD105) is a proliferation-associated surface protein expressed by human vascular endothelial cells. It is a co-receptor for transforming growth factor (TGF) -β1 and TGF-β3, and plays a major role in angiogenesis. Upregulation of endoglin has been reported in endothelial cells of breast and colorectal cancers, and elevated levels of serum endoglin have been associated with tumor metastasis in breast cancer patients. Materials and Methods: Pretreatment EDTA plasma from 224 metastatic breast cancer patients enrolled in a phase III 2nd-line hormone therapy trial and 50 healthy post-menopausal female controls were assayed for soluble endoglin using a double-antibody sandwich ELISA from R&D Systems (Minneapolis, MN). Results: In the post-menopausal female control group (n=50), the mean ± SD for plasma endoglin levels were 5.00 ± 1.84 ng/ml, with a range of 2.38–9.83 ng/ml. The upper limit of normal was defined as the mean + 2 SD (8.7 ng/ml) for plasma endoglin. In the breast cancer patient group, the mean ± SD for plasma endoglin was 6.40 ± 2.23 ng/ml, with a range of 3.00–19.79 ng/ml. Elevated plasma endoglin levels were detected in 26 of 224 patients (11.6%). Patients with elevated vs. normal plasma endoglin levels had a reduced clinical benefit rate (CR +PR+Stable)(15% vs. 42%)(p=0.01) to hormone therapy. Time to progression (TTP) was shorter for patients with elevated vs. normal plasma endoglin levels, but did not reach statistical significance (p=0.2). Patients with elevated plasma endoglin had decreased overall survival (median 645 days vs. 947 days)(p=0.005). Another plasma angiogenic marker, soluble Tie-2 receptor, did not significantly correlate with clinical outcome. A weak correlation existed between plasma endoglin and Tie-2 (r =.54, p<0.00001). There was no correlation between plasma endoglin levels and the presence of bone metastasis vs. other sites of metastases. Conclusions: Elevated pretreatment plasma endoglin levels predicted for decreased clinical benefit rate to 2nd-line hormone therapy and a shorter overall survival in metastatic breast cancer patients. Circulating endoglin levels deserve further study for monitoring anti-angiogenic therapy. [Table: see text]