Background: The role of estrogen receptor beta (ER-b) in human breast cancer remains unclear. There is no consensus regarding the clinical utility of an ER-b assay. Some studies have suggested that ER-b may oppose actions of estrogen receptor alpha (ER-a) in breast cancer cells and clinical evidences indicate that loss of ER-b expression is associated with a poor prognosis and resistance to endocrine therapy. Tumor expression of the Ki67 antigen is used to assess the prognosis of cancer patients. A change in the expression of Ki67 after short-term exposure of patients to therapeutic agents is frequently used as a proliferation marker of treatment efficacy. The association between ER-b and HER-2, the human epidermal growth factor receptor 2 used in the clinical setting as a prognostic and predictive marker, in breast tumors remains unclear.

Objectives: The aim of this study was to compare the expression of Ki-67, HER-2, ER-a and ER-b in postmenopausal women with invasive ductal carcinomas (IDC), prior and after tamoxifen and anastrozole in neoadjuvant short-time treatment.

Material and Methods: Patients were double-blind randomized in a prospective placebo controlled study with three neoadjuvant hormone therapy (HT) groups. To determine the clinical significance of the tumor cell proliferation during endocrine therapy for breast cancer, we measured the expression of Ki67 in tumor biopsy samples taken before and after 26 days of presurgical treatment with anastrozole 1mg/day (n= 25) or tamoxifen 20mg/day (n= 24) or placebo (n=29) in 78 patients with primary palpable IDC (stage II and III). Pre and post HT samples were disposed in tissue micro array blocks and submitted to immunohistochemical essay. Biomarkers status (Ki-67, HER-2, ER-a and ER-b) were obtained comparing each immunohistochemical evaluation of pre and post-surgery samples using semi-quantitative Allred's method. Statistical analysis were performed using the GEE (General Estimation Equations) and Anova tests with significant p < 0,05.

Results: Randomization was adequate. HER2 did not show any variation in the three groups evaluated. With positive ER-b (Allred's score 3 to 8), only anastrozole group showed a significant reduction in KI-67 status from 4.46 in the pre-treatment to 3.15 in post treatment samples (p=0.0130). Positive ER-a breast cancers showed a significant reduction in KI-67 status in tamoxifen and anastrozole groups, and this reduction was correlated to a positive ER-b score.

Discussion: Clinical management of breast cancer is guided by assessment of some tumor parameters. One of these is estrogen receptor status. With the discovery of ER-b, definition of ER status is potentially more complex. Our study brings new data about the short-time exposure to endocrine therapy. The role of ER-a may be different when co-expressed with ER-b and ER-b signaling may be a therapeutic target in these tumors.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-06-07.