Department of Breast Surgery, Fudan University Shanghai Cancer Center, 270 Dong An Road, 200032, Shanghai, China.
Cancer Lett. 2011 Mar 1;302(1):63-8. doi: 10.1016/j.canlet.2010.12.014. Epub 2011 Jan 8.
Clinical data suggest that the estrogen receptor (ER) contributes to chemotherapeutic responsiveness. However, ER status alone is not consistently predictive. In this study, we used a microarray approach to find novel ER-related genes that predicted chemotherapy responses, with the hope of providing a robust multi-variable prediction method.
One hundred and ten patients with stages II and III breast cancer were included. They received four preoperative cycles of a weekly PCb (paclitaxel plus carboplatin) regimen. A total of 55 training cases were used for marker discovery and for identification of any ER-related genes that may have been associated with a chemotherapeutic response ("training cases"). The other 55 patients were available as an independent validation set ("validation cases") to test, using immunohistochemistry (IHC).
In the training set, 20 significantly differentially expressed genes were identified. Among these 20 genes, TFF1, ESR1, GATA3 and TFF3 were found to be ER-related. Among 55 independent validation cases, univariate analysis indicated that clinical variables and ER-related genes were all significantly associated with pCR. It was shown that the pCR rate was as high as 80% when these five factors were all negative. In contrast, these five factors were all positive in seven of nine chemo-resistant patients.
In conjunction with levels of ER-related genes, expression of ER protein may provide important predictive outcomes for responses to neoadjuvant chemotherapy and may allow for the identification of a subgroup of patients who could significantly benefit from chemotherapy (or who may be resistant to it).
临床数据表明，雌激素受体（ER）有助于化疗反应。然而，ER 状态本身并不具有一致性的预测性。在这项研究中，我们使用微阵列方法寻找新的与 ER 相关的基因，这些基因可预测化疗反应，希望提供一种稳健的多变量预测方法。
共纳入 110 例 II 期和 III 期乳腺癌患者。他们接受了四个术前周期的每周 PCb（紫杉醇加卡铂）方案。总共 55 例训练病例用于标志物发现，并确定任何可能与化疗反应相关的 ER 相关基因（“训练病例”）。另外 55 例患者可作为独立验证集（“验证病例”），通过免疫组织化学（IHC）进行测试。
在训练集中，鉴定出 20 个差异表达显著的基因。在这 20 个基因中，TFF1、ESR1、GATA3 和 TFF3 被发现与 ER 相关。在 55 例独立验证病例中，单变量分析表明，临床变量和 ER 相关基因均与 pCR 显著相关。当这五个因素均为阴性时，pCR 率高达 80%。相比之下，在 9 例化疗耐药患者中，有 7 例患者的这五个因素均为阳性。
与 ER 相关基因的水平相结合，ER 蛋白的表达可能为新辅助化疗的反应提供重要的预测结果，并可能识别出一组可能从化疗中显著受益（或可能对其产生耐药性）的患者。
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