Background:Endo180 (CD280; MRC2; uPARAP)-dependent collagen remodelling is dysregulated in primary tumours and bone metastasis. Here, we confirm the release and diagnostic accuracy of soluble Endo180 for diagnosing metastasis in breast cancer (BCa).Methods:Endo180 was quantified in BCa cell conditioned medium and plasma from BCa patients stratified according to disease status and bisphosphonate treatment (n=88). All P-values are from two-sided tests.Results:Endo180 is released by ectodomain shedding from the surface of MCF-7 and MDA-MB-231 BCa cell lines. Plasma Endo180 was significantly higher in recurrent/metastatic (1.71±0.87; n=59) vs early/localised (0.92±0.37; n=29) BCa (P<0.0001). True/false-positive rates for metastasis classification were: 85%/50% for the reference standard, CA 15-3 antigen (28 U ml−1); ⩽97%/⩾36% for Endo180; and ⩽97%/⩾32% for CA 15-3 antigen+Endo180. Bisphosphonate treatment was associated with reduced Endo180 levels in BCa patients with bone metastasis (P=0.011; n=42). True/false-positive rates in bisphosphonate-naive patients (n=57) were: 68%/45% for CA 15-3 antigen; ⩽95%/⩾20% for Endo180; and ⩽92%/⩾21% for CA 15-3 antigen+Endo180.Conclusion:Endo180 is a potential marker modulated by bisphosphonates in metastatic BCa.

Purpose: To establish whether the collagen remodelling receptor, Endo180, should be given consideration as a useful plasma marker in metastatic breast cancer. Patients and Methods: Analysis of MCF-7 and MDA-MB-231 cell conditioned medium validated the anti-human (39.10) monoclonal antibody as suitable for the detection of soluble Endo180 in plasma. Eighty-seven breast cancer patients with early primary, locally advanced and metastatic disease were included in the study. Correlations between Endo180, CA 15–3 antigen (MUC1; mucin 1) and bisphosphonate treatment were investigated. Results: Endo180 was elevated in metastatic compared to early breast cancer (P &lt;.0001) and was able to differentiate locoregional disease and visceral and/or osseous metastasis (P = .0005). In combination CA 15–3 antigen (cut-off: 28 U/mL) and Endo180 (relative plasma level cut-off range: 0.95–1.65) had sensitivity of 94–97% and specificity of 52–68%. Endo180 levels were significantly higher in patients who were treatment naive (2.17 ± 0.82, N = 13) compared to those previously (1.82 ± 0.33, N = 5) or currently (1.37 ± 0.74, N = 24) receiving bisphosphonates (P = .011). In the bisphosphonate naive setting (N = 57) the combination of Endo180 (relative plasma level cut-off range: 0.95–1.65) and CA 15–3 antigen (cut-off: 28 U/mL) had a sensitivity of 87–92% and specificity of 72–79%. Conclusion: Endo180 is a plasma marker with high sensitivity in metastatic breast cancer that can be modulated by bisphosphonate treatment. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-02-03.