Wnt pathway is affected by endocrine therapy in breast carcinomas

Abstract

Background and aim: Identifying potential predictive biomarkers of response to endocrine therapy would benefit most estrogen receptor-positive (ER+) breast cancer patients. Our aim was to compare the expression of the wingless type (Wnt) pathway-related proteins (adenomatous polyposis coli [APC], E-cadherin, beta-catenin, cyclin D1, and c-myc) in postmenopausal women with ER+ invasive ductal carcinomas (IDC), prior to and after tamoxifen (n= 18) or anastrozole (n= 15) treatment, in a double-blind, placebo-controlled (n= 25), prospective study for 26 days prior to surgery. Methods: Tissue microarray blocks were constructed from pre- and post-treatment biopsy samples. Nuclear immunostaining of c-myc, APC, estrogen and progesterone receptor levels were assessed using the Allred scoring system, and cytoplasmic immunostaining of cyclin D1, beta-catenin and E-cadherin was assessed with the Hercep-Test system. An anova statistical analysis estimated general equations and analysis of variance with a significance level of 0.05. Results: Tamoxifen increased c-myc (P= 0.0061) and APC (P= 0.0452) expression. Anastrozole did not significantly affect expression of any Wnt-related proteins. Conclusions: In post-menopausal ER+ IDC, tamoxifen for 26 days prior to IDC surgery influenced statistically the expression of important cell cycle regulators as APC and c-myc, whereas anastrozole therapy did not interfere with this pathway during the same period. These Wnt related proteins may contribute to selective estrogen receptor modulator resistance.