Receptor de estrogênio beta como marcador preditivo de resposta no tratamento neoadjuvante do carcinoma de mama com anastrozol e tamoxifeno

• Ano de defesa: 2014
• Autor(a) principal: Madeira, Marcelo [UNIFESP]
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: cancer; estrogen receptor beta; receptor de estrogênio beta; receptor de estrogênio alfa; câncer de mama; tamoxifeno; inibidores da aromatase; terapia neoadjuvante
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=1775900; https://repositorio.unifesp.br/handle/11600/46388

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 is 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, the expression of Ki67 was measured 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 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: These 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.