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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

Marcelo Madeira12*, André Mattar13, Ângela Flávia Logullo4, Fernando Augusto Soares5 and Luiz Henrique Gebrim13

Author Affiliations

1 Senology Discipline, Department of Gynecology, Federal University of Sao Paulo-UNIFESP, R. Botucatu, 740, 04023-900 Sao Paulo, SP, Brazil

2 Department of Obstetrics & Gynecology and Women’s Health of Albert Einstein Hospital, Av. Albert Einstein, 627, 05652-900 Sao Paulo, SP, Brazil

3 Department of Breast Medical Oncology, Centro de Referência da Saúde da Mulher (CRSM)-Pérola Byington Hospital, Av. Brigadeiro Luis Antonio, 683, 01317-000 Sao Paulo, SP, Brazil

4 Department of Pathology, Federal University of Sao Paulo-UNIFESP, R. Botucatu, 740, 04023-062 Sao Paulo, SP, Brazil

5 Department of Pathology, AC Camargo Hospital, R. Professor Antonio Prudente, 211, 01509-010 Sao Paulo, SP, Brazil

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BMC Cancer 2013, 13:425  doi:10.1186/1471-2407-13-425

Published: 18 September 2013



The 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.


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-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.


The 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).


Our 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 registration

Current Controlled Trials ISRCTN89801719

Estrogen receptor beta; Breast cancer; Estrogen receptor; Aromatase inhibitors/Anastrozole; Tamoxifen; Ki67; Neoadjuvant therapy; Tumor markers