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

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

Author Madeira, Marcelo Autor UNIFESP Google Scholar
Mattar, Andre Autor UNIFESP Google Scholar
Logullo, Angela Flavia Autor UNIFESP Google Scholar
Soares, Fernando Augusto Google Scholar
Gebrim, Luiz Henrique Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Albert Einstein Hosp
Perola Byington Hosp
AC Camargo Hosp
Abstract Background: the role of estrogen receptor beta (ER-beta) in breast cancer (BC) remains unclear. Some studies have suggested that ER-beta may oppose the actions of estrogen receptor alpha (ER-alpha), and clinical evidence has indicated that the loss of ER-beta 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-beta and the ER-alpha/ER-beta ratio in predicting the response to endocrine therapy and whether different regimens have any effect on ER-beta expression levels.Methods: Ninety 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-beta, ER-alpha 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.Results: the frequency of ER-beta expression did not change after treatment (p = 0.33). There were no significant changes in Ki67 levels in ER-beta-negative cases (p = 0.45), but in the ER-beta-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-alpha and ER-beta expression levels. Only patients with an ER-alpha/ER-beta 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).Conclusions: Our results provide additional data that indicate that the measurement of ER-beta 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-alpha/ER-beta expression.
Keywords Estrogen receptor beta
Breast cancer
Estrogen receptor
Aromatase inhibitors/Anastrozole
Tamoxifen
Ki67
Neoadjuvant therapy
Tumor markers
Language English
Date 2013-09-18
Published in Bmc Cancer. London: Biomed Central Ltd, v. 13, 12 p., 2013.
ISSN 1471-2407 (Sherpa/Romeo, impact factor)
Publisher Biomed Central Ltd
Extent 12
Origin http://dx.doi.org/10.1186/1471-2407-13-425
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000325869200001
URI http://repositorio.unifesp.br/handle/11600/36759

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