Background: Identification of new biomarkers with potential predictive and prognostic role has contributed unequivocally to breast cancer treatment. Although traditionally endocrine therapy is based on Hormonal receptors status (estrogen - ER and progesterone- PR), some patients become hormone resistant. In order to identify a possible profile associated to hormonal resistance, some biomarkers have been assessed after short period primary hormone therapy (HT).Objectives: To compare the expression of Ki-67, Bcl2, Bax, Bak, ER and e PR in postmenopausal women with ER positive invasive ductal carcinomas (IDC), prior and after tamoxifen and anastrozole in neoadjuvant treatment.Methods: Fifty-eight patients with palpable ER-positive IDC (stage II and III) were double-blind randomized in a prospective placebo controlled study with three neoadjuvant HT groups for twenty-six days prior to surgical treatment: Anastrozole 1mg/day (n= 18), Placebo (n=25) and Tamoxifen 20mg/day (n= 15). Pre and post HT samples were disposed in tissue micro array blocks and submitted to immunohistochemical essay. Biomarkers status (Ki-67, Bcl2, Bax, Bak, ER and e PR) 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: ER and PR status did not change significantly in placebo group (96% -96% and 76-72%) and KI-67 index variation was 40 to 52% (p>0,05), as expected. In Tamoxifen group, ER status was also stable during treatment (100-100%). However, in anastrozole group, ER status -originally 100% - lowered to 89%,(p>0,05) and also PR expression rates lowered significantly from 56% to 28% in post treatment (p=0,0007). Anastrozole group also showed a significant reduction in KI-67 status from 78% in the pre-treatment KI-67 to 39% in post treatment samples (p=0,0079). Tamoxifen group showed a slight increase of PR expression from 73% to 93% along a non-statistical significant variation of KI-67 status 67% pre-treatment to 47% post-treatment. The other biomarkers (RE, Bak, Bax, Bcl-2 )did not show any variation in the three groups evaluated.Conclusions: a significant reduction of PR and ki-67 status was associated to Anastrozol treatment (26 days, 1mg/day). Short primary HT was not associated to any variation in apoptosis-related proteins (Bak, Bax, Bcl-2) regardless the drug used.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2145.

2009