Department of Gynecology, Federal University of São Paulo (UNIFESP), Rua Napoleão de Barros, 715 - 7°.andar, CEP 04024-002, São Paulo, SP, Brazil.
J Cancer Res Clin Oncol. 2011 May;137(5):897-905. doi: 10.1007/s00432-010-0950-4. Epub 2010 Oct 1.
The objective of this study was to compare Ki-67, Bcl-2, Bax, Bak, ER, and PgR expression in postmenopausal women with ER-positive invasive breast cancer (IBC) before and after short-term hormone therapy (HT) with either tamoxifen or anastrozole in order to identify a possible biomarker profile associated with hormone resistance.
Fifty-eight patients with palpable IBC were assigned to receive neoadjuvant therapy with either anastrozole, placebo, or tamoxifen for 26 days prior to surgery. Tissue microarray blocks were constructed from pre- and post-treatment biopsy samples and used for immunohistochemical analysis. Biomarker (Ki-67, Bcl-2, Bax, Bak, ER, and PgR) levels were assessed semiquantitatively using the Allred score. A statistical analysis was performed using general estimating equations (GEE) and analysis of variance (ANOVA) with a significance level of 0.05.
There was a significant reduction in PgR scores from baseline (mean, 4.22) to post-treatment (mean, 1.94) in the anastrozole group, but only a non-significant trend toward an increase in PgR scores was found in the tamoxifen group. There was a significant reduction in Ki-67 scores from baseline (mean, 3.61) to post-treatment (mean, 2.56) in the anastrozole group (P = 0.01), but only a non-significant trend toward a reduction in Ki-67 scores was found in the tamoxifen group.
There was a significant reduction in PgR and Ki-67 expression in the group treated with anastrozole. In the present study, the short-term HT was not associated with changes in apoptosis-related protein levels, regardless the type of drug used.
本研究旨在比较短期激素治疗(HT)前后绝经后 ER 阳性浸润性乳腺癌(IBC)患者 Ki-67、Bcl-2、Bax、Bak、ER 和 PgR 的表达,以确定与激素抵抗相关的可能生物标志物谱。
将 58 例可触及的 IBC 患者分配接受新辅助治疗,分别接受阿那曲唑、安慰剂或他莫昔芬治疗 26 天,然后进行手术。从治疗前后的活检样本中构建组织微阵列块,并进行免疫组织化学分析。使用 Allred 评分半定量评估生物标志物(Ki-67、Bcl-2、Bax、Bak、ER 和 PgR)水平。使用一般估计方程(GEE)和方差分析(ANOVA)进行统计分析,显著性水平为 0.05。
阿那曲唑组的 PgR 评分从基线(均值,4.22)显著降低到治疗后(均值,1.94),而他莫昔芬组的 PgR 评分仅呈非显著升高趋势。阿那曲唑组的 Ki-67 评分从基线(均值,3.61)显著降低到治疗后(均值,2.56)(P = 0.01),而他莫昔芬组的 Ki-67 评分仅呈非显著降低趋势。
阿那曲唑组的 PgR 和 Ki-67 表达显著降低。在本研究中,短期 HT 与使用的药物类型无关,与凋亡相关蛋白水平的变化无关。