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.
BackgroundEpidemiological studies have reported positive associations between anthropometric measures and risk for developing breast cancers that express hormone receptors and associated mortality. However, the impact of nutritional status on the molecular response to endocrine therapy has yet to be described.MethodsBody mass index (BMI), waist circumference (WC), hip circumference (HP), and waist-to-hip ratio (WHR) were measured in patients with invasive ductal carcinoma (IDC) before and after neoadjuvant treatment with either tamoxifen or anastrozole, and a possible correlation with prognostic factors, as estrogen receptor (ER), progesterone receptor (PgR), and proliferative index (Ki-67), was analyzed. Fifty-seven patients with palpable ER-positive IDC were randomized into three neoadjuvant treatment groups and received anastrozole or placebo or tamoxifen for twenty-one days. Biomarker status was obtained by comparing the immunohistochemical evaluation of samples collected before and after treatment, using the Allred scoring system. Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS).Results and ConclusionsAfter treatment, the anastrozole group showed reduced ER and PgR expression (p < 0.05), and both the anastrozole and tamoxifen groups showed lower Ki-67 status. A significant reduction in PgR positivity (p < 0.05) was found in women with large WC and HC who were treated with anastrozole. Reduction in PgR positivity also tended to be associated with BMI (p = 0.09) in the anastrozole group. BMI, WC, HC and WHR correlated neither with biomarker levels in the tamoxifen and placebo groups nor with ER and Ki-67 status in the anastrozole group after primary endocrine treatment.
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