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

BMC Cancer

Marcelo Madeira⁴  André Mattar³  Ângela Flávia Logullo²  Fernando Augusto Soares¹  Luiz Henrique Gebrim³ 

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

[2] Department of Pathology, Federal University of Sao Paulo-UNIFESP, R. Botucatu, 740, 04023-062 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 Obstetrics & Gynecology and Women’s Health of Albert Einstein Hospital, Av. Albert Einstein, 627, 05652-900 Sao Paulo, SP, Brazil

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

Others  :  1079565
DOI  :  10.1186/1471-2407-13-425

 received in 2013-04-15, accepted in 2013-09-16,  发布年份 2013

【 摘 要 】

Background

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.

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-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.

Results

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).

Conclusions

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

【 授权许可】

   
2013 Madeira et al.; licensee BioMed Central Ltd.

【 图 表 】

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