COX-2 expression is predictive for early relapse and aromatase inhibitor resistance in patients with ductal carcinoma in situ of the breast, and is a target for treatment

34Citations
Citations of this article
89Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

Background:Stratification of patients for treatment of ductal carcinoma in situ (DCIS) is suboptimal, with high systemic overtreatment rates.Methods:A training set of 95 tumours from women with pure DCIS were immunostained for proteins involved in cell survival, hypoxia, growth factor and hormone signalling. A generalised linear regression with regularisation and variable selection was applied to a multiple covariate Cox survival analysis with recurrence-free survival 10-fold cross-validation and leave-one-out iterative approach were used to build and test the model that was validated using an independent cohort of 58 patients with pure DCIS. The clinical role of a COX-2-targeting agent was then tested in a proof-of-concept neoadjuvant randomised trial in ER-positive DCIS treated with exemestane 25 mg day-1 ±celecoxib 800 mg day-1.Results:The COX-2 expression was an independent prognostic factor for early relapse in the training (HR 37.47 (95% CI: 5.56-252.74) P=0.0001) and independent validation cohort (HR 3.9 (95% CI: 1.8-8.3) P=0.002). There was no significant interaction with other clinicopathological variables. A statistically significant reduction of Ki-67 expression after treatment with exemestane±celecoxib was observed (P<0.02) with greater reduction in the combination arm (P<0.004). Concomitant reduction in COX-2 expression was statistically significant in the exemestane and celecoxib arm (P<0.03) only.Conclusions:In patients with DCIS, COX-2 may predict recurrence, aiding clinical decision making. A combination of an aromatase inhibitor and celecoxib has significant biological effect and may be integrated into treatment of COX2-positive DCIS at high risk of recurrence. © 2014 Cancer Research UK.

Cite

CITATION STYLE

APA

Generali, D., Buffa, F. M., Deb, S., Cummings, M., Reid, L. E., Taylor, M., … Fox, S. B. (2014). COX-2 expression is predictive for early relapse and aromatase inhibitor resistance in patients with ductal carcinoma in situ of the breast, and is a target for treatment. British Journal of Cancer, 111(1), 46–54. https://doi.org/10.1038/bjc.2014.236

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free