Presence of Foxp3 expression in tumor cells predicts better survival in HER2-overexpressing breast cancer patients treated with neoadjuvant chemotherapy
Presence of Foxp3 expression in tumor cells predicts better survival in HER2-overexpressing breast cancer patients treated with neoadjuvant chemotherapy
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DOI：
10.1007/s10549-010-0831-1
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发表时间：
2011-01-01
影响因子：
3.8
通讯作者：
Ghiringhelli, Francois
中科院分区：
文献类型：
--
作者：
Ladoire, Sylvain;Arnould, Laurent;Ghiringhelli, Francois
叉头盒蛋白3不仅在调节性T细胞中高度表达，而且在肿瘤细胞中高度表达，作为乳腺癌基因（包括HER 2）的转录阻遏物。我们在一个接受新辅助化疗的HER 2过表达乳腺癌患者的大队列中研究了癌细胞Foxp 3表达的预后意义。在103例原发性浸润性HER 2过表达乳腺癌患者中，通过免疫组织化学检测Foxp 3阳性肿瘤细胞，并接受新辅助化疗（联合或不联合曲妥珠单抗）。Kaplan-Meier分析和考克斯回归模型分别用于评估无复发生存期和总生存期，并根据肿瘤细胞中Foxp 3表达的存在或不存在进行评估。57%的乳腺癌细胞为Foxp 3+。乳腺癌细胞中Foxp 3表达与更好的无复发（P = 0.005）和总生存期（P = 0.03）相关。通过多变量分析，Foxp 3+肿瘤细胞的存在产生了更好的无复发（P = 0.006）和总生存（P = 0.03）的独立预后因素。这些研究结果表明，Foxp 3+肿瘤细胞的存在代表了HER 2过表达乳腺癌预后改善的一个新的独立预后因素，这可能有助于识别新辅助化疗后接受额外治疗的高风险患者。
The Forkhead Box Protein 3 is highly expressed not only in regulatory T cells, but also in tumor cells, acting as a transcriptional repressor of breast oncogenes including HER2. We investigated the prognostic significance of Foxp3 expression in cancer cells in a large cohort of patients with HER2-overexpressing breast carcinoma treated with neoadjuvant chemotherapy. Foxp3-positive tumor cells were detected by immunohistochemistry in 103 patients with primary invasive HER2-overexpressing breast carcinoma, and treated with neoadjuvant chemotherapy, with or without trastuzumab. Kaplan-Meier analysis and Cox regression model were used to assess relapse-free and overall survival, respectively, and according to the presence or the absence of Foxp3 expression in tumor cells. Breast cancer cells were Foxp3+ in 57% of tumors. Foxp3 expression in breast cancer cells was associated with better relapse-free (P = 0.005) and overall survival (P = 0.03). By multivariate analysis, the presence of Foxp3+ tumor cells produced an independent prognostic factor for both better relapse-free (P = 0.006) and overall survival (P = 0.03). These findings indicate that the presence of Foxp3+ tumor cells represents a new independent prognostic factor of improved outcome in HER2-overexpressing breast carcinoma, which could help identify high-risk patients for additional therapies after neoadjuvant chemotherapy.