Esteva Francisco J, Wang Jing, Lin Feng, Mejia Jaime A, Yan Kai, Altundag Kadri, Valero Vicente, Buzdar Aman U, Hortobagyi Gabriel N, Symmans W Fraser, Pusztai Lajos
Department of Breast Medical Oncology, Unit 1354, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Breast Cancer Res. 2007;9(6):R87. doi: 10.1186/bcr1836.
We performed gene expression analysis to identify molecular predictors of resistance to preoperative concomitant trastuzumab and paclitaxel followed by 5-fluorouracil, epirubicin, and cyclophosphamide (T/FEC).
Pretreatment fine-needle aspiration specimens from 45 patients with HER-2-overexpressing stage II to IIIA breast cancer were subjected to transcriptional profiling and examined for differential expression of various genes and gene sets. The primary endpoint for tumor response was pathologic complete response (pCR). Correlations between pCR and gene expression were sought.
The overall pCR rate was 64%. Age, nuclear grade, tumor size, nodal status, quantitative expression of estrogen and HER-2 receptor mRNA, and HER-2 gene copy number showed no correlation with pCR. Results of gene set enrichment analysis suggested that the lower expression of genes involved with CD40 signaling is associated with a greater risk of residual cancer after the preoperative chemotherapy that includes trastuzumab.
CD40 signaling may play a role in determining response to trastuzumab-plus-T/FEC therapy in patients with HER-2-overexpressing breast cancer.
我们进行了基因表达分析，以确定对术前曲妥珠单抗联合紫杉醇治疗，随后进行5-氟尿嘧啶、表柔比星和环磷酰胺（T/FEC）治疗产生耐药的分子预测指标。
对45例HER-2过表达的II至IIIA期乳腺癌患者的预处理细针穿刺标本进行转录谱分析，并检测各种基因和基因集的差异表达。肿瘤反应的主要终点是病理完全缓解（pCR）。研究pCR与基因表达之间的相关性。
总体pCR率为64%。年龄、核分级、肿瘤大小、淋巴结状态、雌激素和HER-2受体mRNA的定量表达以及HER-2基因拷贝数与pCR均无相关性。基因集富集分析结果表明，与CD40信号传导相关的基因表达较低，与包括曲妥珠单抗在内的术前化疗后残留癌症风险较高相关。
CD40信号传导可能在决定HER-2过表达乳腺癌患者对曲妥珠单抗加T/FEC治疗的反应中起作用。
