Chang Jenny C, Makris Andreas, Gutierrez M Carolina, Hilsenbeck Susan G, Hackett James R, Jeong Jennie, Liu Mei-Lan, Baker Joffre, Clark-Langone Kim, Baehner Frederick L, Sexton Krsytal, Mohsin Syed, Gray Tara, Alvarez Laura, Chamness Gary C, Osborne C Kent, Shak Steven
Breast Center and the Department of Medicine, Baylor College of Medicine and the Methodist Hospital, 1 Baylor Plaza, MS 600, Houston, TX 77030, USA.
Breast Cancer Res Treat. 2008 Mar;108(2):233-40. doi: 10.1007/s10549-007-9590-z. Epub 2007 Apr 28.
Previously, we had identified gene expression patterns that predicted response to neoadjuvant docetaxel. Other studies have validated that a high Recurrence Score (RS) by the 21-gene RT-PCR assay is predictive of worse prognosis but better response to chemotherapy. We investigated whether tumor expression of these 21 genes and other candidate genes can predict response to docetaxel. Core biopsies from 97 patients were obtained before treatment with neoadjuvant docetaxel (4 cycles, 100 mg/m2 q3 weeks). Three 10-microm FFPE sections were submitted for quantitative RT-PCR assays of 192 genes that were selected from our previous work and the literature. Of the 97 patients, 81 (84%) had sufficient invasive cancer, 80 (82%) had sufficient RNA for QRTPCR assay, and 72 (74%) had clinical response data. Mean age was 48.5 years, and the median tumor size was 6 cm. Clinical complete responses (CR) were observed in 12 (17%), partial responses in 41 (57%), stable disease in 17 (24%), and progressive disease in 2 patients (3%). A significant relationship (P<0.05) between gene expression and CR was observed for 14 genes, including CYBA. CR was associated with lower expression of the ER gene group and higher expression of the proliferation gene group from the 21 gene assay. Of note, CR was more likely with a high RS (P=0.008). We have established molecular profiles of sensitivity to docetaxel. RT-PCR technology provides a potential platform for a predictive test of docetaxel chemosensitivity using small amounts of routinely processed material.
此前，我们已确定了可预测对新辅助多西他赛反应的基因表达模式。其他研究已证实，通过21基因RT-PCR检测得出的高复发评分（RS）预示着预后较差，但对化疗的反应较好。我们研究了这21个基因以及其他候选基因的肿瘤表达是否能预测对多西他赛的反应。在新辅助多西他赛治疗（4个周期，100mg/m²，每3周一次）前，获取了97例患者的核心活检样本。提交了3张10微米的福尔马林固定石蜡包埋（FFPE）切片，用于对从我们之前的研究及文献中挑选出的192个基因进行定量RT-PCR检测。97例患者中，81例（84%）有足够的浸润性癌组织，80例（82%）有足够的RNA用于QRT-PCR检测，72例（74%）有临床反应数据。平均年龄为48.5岁，肿瘤大小中位数为6cm。观察到12例（17%）临床完全缓解（CR），41例（57%）部分缓解，17例（24%）疾病稳定，2例（3%）疾病进展。观察到包括CYBA在内的14个基因的基因表达与CR之间存在显著关系（P<0.05）。CR与21基因检测中ER基因组的低表达及增殖基因组的高表达相关。值得注意的是，高RS时更可能出现CR（P=0.008）。我们已建立了对多西他赛敏感性的分子图谱。RT-PCR技术为使用少量常规处理材料进行多西他赛化疗敏感性预测检测提供了一个潜在平台。
