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


BACKGROUND
NCT00002864, http://clinicaltrials.gov/show/NCT00002864.
Vivien H C
VH
Bramwell
Alan B
AB
Tuck
Judith-Anne W
JA
Chapman
Pieter H
PH
Anborgh
Carl O
CO
Postenka
Waleed
W
Al-Katib
Lois E
LE
Shepherd
Lei
L
Han
Carolyn F
CF
Wilson
Kathleen I
KI
Pritchard
Michael N
MN
Pollak
Ann F
AF
Chambers
D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood*; D015282:Octreotide / Q000627:therapeutic use; D053495:Osteopontin / Q000097:blood*; D013629:Tamoxifen / Q000627:therapeutic use
D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D013629:Tamoxifen; D053495:Osteopontin; D015282:Octreotide