Assessment of osteopontin in early breast cancer: correlative study in a randomised clinical trial

Vivien H C Bramwell, Alan B Tuck, Judith-Anne W Chapman, Pieter H Anborgh, Carl O Postenka, Waleed Al-Katib, Lois E Shepherd, Lei Han, Carolyn F Wilson, Kathleen I Pritchard, Michael N Pollak, Ann F Chambers, Vivien H C Bramwell, Alan B Tuck, Judith-Anne W Chapman, Pieter H Anborgh, Carl O Postenka, Waleed Al-Katib, Lois E Shepherd, Lei Han, Carolyn F Wilson, Kathleen I Pritchard, Michael N Pollak, Ann F Chambers

Abstract

Introduction: Osteopontin (OPN) is a malignancy-associated glycoprotein that contributes functionally to tumor aggressiveness. In metastatic breast cancer, we previously demonstrated that elevated OPN in primary tumor and blood was associated with poor prognosis.

Methods: We measured OPN in plasma by ELISA, and in tumors by immunohistochemistry, in 624 (94%) and 462 (69%), respectively, of 667 postmenopausal women with hormone responsive early breast cancer treated by surgery followed by adjuvant treatment with tamoxifen +/- octreotide in a randomized trial (NCIC CTG MA.14; National Cancer Institute of Canada Clinical Trials Group Mammary.14).

Results: Plasma OPN was measured in 2,540 samples; 688 at baseline and 1,852 collected during follow-up. Mean baseline plasma OPN was 46 ng/ml (range 22.6 to 290) which did not differ from normal levels. Mean percentage OPN tumor cell positivity was 33.9 (95% CI: 30.2 to 37.9). There was no correlation between plasma and tumor OPN values. In multivariate analysis, neither was associated with event-free survival (EFS), relapse-free survival (RFS), overall survival (OS), bone RFS or non-bone RFS. An exploratory analysis in patients with recurrence showed higher mean OPN plasma levels 60.7 ng/ml (23.9 to 543) in the recurrence period compared with baseline levels.

Conclusions: The hypothesis that OPN tumor expression would have independent prognostic value in early breast cancer was not supported by multivariate analysis of this study population. Plasma OPN levels in women with hormone responsive early breast cancer in the MA.14 trial were not elevated and there was no evidence for prognostic value of plasma OPN in this defined group of patients. However, our finding of elevated mean OPN plasma level around the time of recurrence warrants further study.

Trial registration: NCT00002864, https://ichgcp.net/clinical-trials-registry/NCT00002864.

Figures

Figure 1
Figure 1
Characterization of plasma OPN by group. This figure visually compares plasma OPN levels of healthy women (A = 90 pts) with levels in women who never had recurrence, at baseline (B = 304 pts) and after baseline (E = 456 pts); and with levels in women who had recurrence, at baseline (C = 84 pts), in Period 1 (D = 100 pts) and Period 2 (F = 80 pts). The boxes show OPN values between the 25th and 75th percentiles, with whiskers showing ranges. OPN, osteopontin.
Figure 2
Figure 2
Average OPN plasma levels in recurrent period vs non-recurrent period for 66 patients. This figure graphically shows individual patient changes in plasma OPN for 66 patients with recurrence, from the time period prior to recurrence (Period 1) to the recurrence period (Period 2), who had samples available in both time periods. OPN, osteopontin.

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Source: PubMed

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