This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bramwell, V. H.C. Articles by Chambers, A. F. Search for Related Content PubMed PubMed Citation Articles by Bramwell, V. H.C. Articles by Chambers, A. F.

Serial Plasma Osteopontin Levels Have Prognostic Value in Metastatic Breast Cancer

Authors' Affiliations: ¹ Tom Baker Cancer Centre; ² Department of Pharmacology and Therapeutics, University of Calgary; and ³ Cross Cancer Institute, Edmonton, Alberta, Canada; ⁴ Department of Medicine, University of Sydney, Australia and Consultant in Biostatistics, Research Office, Royal North Shore Hospital, Sydney, Australia; ⁵ London Regional Cancer Program; Departments of ⁶ Oncology and ⁷ Pathology, University of Western Ontario, London, Ontario, Canada; and ⁸ Department of Medicine, Queen's University, Kingston, Ontario, Canada

Requests for reprints: Vivien H.C. Bramwell, Tom Baker Cancer Centre, 1331 29th Street Northwest, Calgary, Alberta, T2N 4N2 Canada. Phone: 403-521-3707; Fax: 403-238-1651; E-mail: vivienbr{at}cancerboard.ab.ca.

Purpose: Osteopontin is a malignancy-associated protein measurable in blood and tumor tissue. To evaluate its prognostic value in advanced disease, we conducted a prospective clinical study measuring serial osteopontin plasma levels in women with metastatic breast cancer throughout the course of their disease.

Experimental Design: One hundred fifty-eight women with newly diagnosed metastatic breast cancer were enrolled in the study. Plasma osteopontin was measured using our validated ELISA, at baseline and every 3 to 12 weeks during and after therapy until death. Multivariate time-dependent survival analyses were conducted using models that right censored patient outcomes 3, 6, and 12 months after the last known osteopontin measurement.

Results: Osteopontin was measured in 1,378 samples (median, 9 per patient). Ninety-nine patients had elevated baseline osteopontin (median, 177 ng/mL; range, 1-2,648 ng/mL). In univariate analysis, elevated baseline osteopontin was associated with short survival (P = 0.02). In a multivariate model incorporating standard prognostic factors, baseline osteopontin was significantly associated with survival duration (relative risk, 1.001; P = 0.038). Metastasis-free interval, visceral metastases, and Eastern Cooperative Oncology Group status 2 to 4 also retained significance. In a multivariate model incorporating standard prognostic factors and changes in sequential osteopontin levels, an osteopontin increase of >250 ng/mL at any time was the variable with the most prognostic value for poor survival (relative risk, 3.26; P = 0.0003), and poor Eastern Cooperative Oncology Group status also retained significance.

Conclusions: This is the first study to show that in women with metastatic breast cancer, increases in osteopontin levels over time are strongly associated with poor survival. Sequential monitoring of osteopontin may have use in making treatment decisions for these patients.

This article has been cited by other articles:

				P. C. Mack, M. W. Redman, K. Chansky, S. K. Williamson, N. C. Farneth, P. N. Lara Jr, W. A. Franklin, Q.-T. Le, J. J. Crowley, and D. R. Gandara Lower Osteopontin Plasma Levels Are Associated With Superior Outcomes in Advanced Non-Small-Cell Lung Cancer Patients Receiving Platinum-Based Chemotherapy: SWOG Study S0003 J. Clin. Oncol., October 10, 2008; 26(29): 4771 - 4776. [Abstract] [Full Text] [PDF]

				M. Suzuki, E. Mose, C. Galloy, and D. Tarin Osteopontin Gene Expression Determines Spontaneous Metastatic Performance of Orthotopic Human Breast Cancer Xenografts Am. J. Pathol., August 1, 2007; 171(2): 682 - 692. [Abstract] [Full Text] [PDF]

				C.-Y. Wu, M.-S. Wu, E.-P. Chiang, C.-C. Wu, Y.-J. Chen, C.-J. Chen, N.-H. Chi, G.-H. Chen, and J.-T. Lin Elevated plasma osteopontin associated with gastric cancer development, invasion and survival Gut, June 1, 2007; 56(6): 782 - 789. [Abstract] [Full Text] [PDF]