Wnt pathway is affected by endocrine therapy in breast carcinomas

Joo, Yong Kyun; Logullo, Ângela Flávia; Mattar, André; Nonogaki, Suely; Soares, Fernando Augusto; Gebrim, Luíz Henrique

doi:10.1111/j.1755-9294.2011.01101.x

Cited by 1 publication

(2 citation statements)

References 43 publications

(68 reference statements)

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“…Tumor TMA blocks were obtained by punching 2-nm tissue cores from each donor paraffin block. The samples were then arrayed onto a recipient blank block using a manual tissue arrayer (Beecher Instruments, Sun Prairie, WI, USA) [ 27 ]. Control tissues were included in each of these paraffin blocks.…”

Section: Methodsmentioning

confidence: 99%

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Estrogen receptor alpha/beta ratio and estrogen receptor beta as predictors of endocrine therapy responsiveness–a randomized neoadjuvant trial comparison between anastrozole and tamoxifen for the treatment of postmenopausal breast cancer

et al. 2013

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BackgroundThe role of estrogen receptor beta (ER-β) in breast cancer (BC) remains unclear. Some studies have suggested that ER-β may oppose the actions of estrogen receptor alpha (ER-α), and clinical evidence has indicated that the loss of ER-β expression is associated with a poor prognosis and resistance to endocrine therapy. The objective of the present study was to determine the role of ER-β and the ER-α/ER-β ratio in predicting the response to endocrine therapy and whether different regimens have any effect on ER-β expression levels.MethodsNinety postmenopausal patients with primary BC were recruited for a short-term double-blinded randomized prospective controlled study. To determine tumor cell proliferation, we measured the expression of Ki67 in tumor biopsy samples taken before and after 26 days of treatment with anastrozole 1 mg/day (N = 25), tamoxifen 20 mg/day (N = 24) or placebo (N = 29) of 78 participants. The pre- and post-samples were placed in tissue microarray blocks and submitted for immunohistochemical assay. Biomarker statuses (ER-β, ER-α and Ki67) were obtained by comparing each immunohistochemical evaluation of the pre- and post-surgery samples using the semi-quantitative Allred’s method. Statistical analyses were performed using an ANOVA and Spearman’s correlation coefficient tests, with significance at p ≤ 0.05.ResultsThe frequency of ER-β expression did not change after treatment (p = 0.33). There were no significant changes in Ki67 levels in ER-β-negative cases (p = 0.45), but in the ER-β-positive cases, the anastrozole (p = 0.01) and tamoxifen groups (p = 0.04) presented a significant reduction in post-treatment Ki67 scores. There was a weak but positive correlation between the ER-α and ER-β expression levels. Only patients with an ER-α/ER-β expression ratio between 1 and 1.5 demonstrated significant differences in Ki67 levels after treatment with anastrozole (p = 0.005) and tamoxifen (p = 0.026).ConclusionsOur results provide additional data that indicate that the measurement of ER-β in BC patients may help predict tamoxifen and anastrozole responsiveness in the neoadjuvant setting. These effects of hormonal treatment appear to be dependent on the ratio of ER-α/ER-β expression.Trial registrationCurrent Controlled Trials ISRCTN89801719

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Section: Methodsmentioning

confidence: 99%

“…0492; DakoCytomation, Carpinteria CA, USA) for 30 min at 37°C. The slides were developed with 0.06% diaminobenzene as the chromogen with 0.06% hydrogen peroxide and counterstained with Harris’ hematoxylin [ 27 ]. Positive and negative control slides were included.…”

Section: Methodsmentioning

confidence: 99%