Predictive value of phosphorylated mammalian target of rapamycin for disease-free survival in breast cancer patients receiving neoadjuvant chemotherapy.
Predictive value of phosphorylated mammalian target of rapamycin for disease-free survival in breast cancer patients receiving neoadjuvant chemotherapy.
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雷帕霉素磷酸化哺乳动物靶点对接受新辅助化疗的乳腺癌患者无病生存的预测价值。
DOI：
10.3892/ol.2014.2551
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发表时间：
2014-12
期刊：
影响因子：
2.9
通讯作者：
Zheng X
中科院分区：
文献类型：
--
作者：
Wang S;Sun Y;He A;Zheng C;Zheng X
哺乳动物靶标雷帕霉素(MTOR)/真核细胞翻译起始因子4E结合蛋白1(4E-BP1)通路在细胞生长、存活和血管生成中起关键作用，已被证明与人表皮生长因子受体2(HER2)状态有关。新辅助化疗(NAC)，也被称为术前治疗，目前已被广泛用于治疗不能手术的局部晚期和炎症性乳腺癌。体外研究表明，mTOR抑制剂与细胞毒剂一起显示出对肿瘤细胞的杀伤活性。在HER2阳性、曲妥珠单抗耐药的转移性乳腺癌中，许多非随机研究揭示了mTOR抑制剂与标准化疗加曲妥珠单抗联合使用时的抗肿瘤活性。本研究分析乳腺癌患者NAC前后磷酸化(P)-mTOR和p-4E-BP1的表达水平，以确定p-mTOR和p-4E-BP1是否影响对NAC的反应和随后的生存。收集83例浸润性导管癌患者的福尔马林固定、石蜡包埋组织，代表配对的核心活检(前-NAC)和手术标本(后-NAC)。采用免疫组织化学方法检测p-mTOR和p-4E-BP1的表达。结果发现，NAC后，p-mTOR和p-4E-BP1的表达下调。NAC后mTOR表达的降低与HER2的表达和肿瘤的缩小呈正相关。P-mTOR和p-4E-BP1在NAC前的高表达与无瘤生存期(DFS)差有关。此外，p-mTOR在NAC后标本中的高表达与较差的DFS相关，无论其在NAC前标本中的表达是高还是低。综上所述，NAC可降低p-mTOR和p-4E-BP1的表达水平。NAC后p-mTOR表达有可能作为DFS的预测指标。然而，需要进一步的研究来阐明磷脂酰肌醇3-激酶/Akt/mTOR/4E-BP1通路在NAC中的作用机制和预测价值。
The mammalian target of rapamycin (mTOR)/eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) pathway plays a critical role in cell growth, survival and angiogenesis, and has been demonstrated to correlate with human epidermal growth factor receptor 2 (HER2) status. Neoadjuvant chemotherapy (NAC), also known as preoperative therapy, is now well established in the treatment of inoperable locally advanced and inflammatory breast cancer. In vitro study has shown that mTOR inhibitors, together with cytotoxic agents, exhibit tumor cell killing activity. A number of non-randomized studies in HER2-positive trastuzumab-resistant metastatic breast cancer have revealed the antitumor activity of mTOR inhibitors when used together with standard chemotherapy plus trastuzumab. In the present study, the expression levels of phosphorylated (p)-mTOR and p-4E-BP1 were analyzed in breast cancer patients prior to and following NAC, to determine whether p-mTOR and p-4E-BP1 affect the response to NAC and the subsequent survival. Formalin-fixed, paraffin-embedded tissues representing matched pairs of core biopsy (pre-NAC) and surgical specimen (post-NAC) from 83 patients with invasive ductal carcinomas were collected. Immunohistochemistry was performed to evaluate the expression of p-mTOR and p-4E-BP1 using a semi-quantitative scoring system by two pathologists. It was found that the expression of p-mTOR and p-4E-BP1 was downregulated following NAC. The decrease in mTOR expression following NAC was found to positively correlate with HER2 expression and the reduction of tumor sizes. The high expression of p-mTOR and p-4E-BP1 in pre-NAC specimens was associated with poor disease-free survival (DFS). Furthermore, the high expression of p-mTOR in post-NAC specimens was associated with poor DFS, regardless of whether the expression was high or low in the pre-NAC specimens. In conclusion, NAC was found to decrease the expression levels of p-mTOR and p-4E-BP1. The p-mTOR expression post-NAC may potentially serve as a predictor for DFS. However, further study is required to clarify the mechanism and to evaluate the predictive value of the phosphatidylinositol 3-kinase/Akt/mTOR/4E-BP1 pathway in NAC.
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影响因子：
8.8
作者：
Coleman, L. J.;Peter, M. B.;Teall, T. J.;Brannan, R. A.;Hanby, A. M.;Honarpisheh, H.;Shaaban, A. M.;Smith, L.;Speirs, V.;Verghese, E. T.;McElwaine, J. N.;Hughes, T. A.
通讯作者：
Hughes, T. A.
影响因子：
3.8
作者：
Kim, Eun-Kyu;Kim, Hyun-Ah;Noh, Woo Chul
通讯作者：
Noh, Woo Chul
影响因子：
3.9
作者：
Ogston, KN;Miller, ID;Heys, SD
通讯作者：
Heys, SD
影响因子：
56.9
作者：
Brunn, GJ;Hudson, CC;Abraham, RT
通讯作者：
Abraham, RT
影响因子：
11.2
作者：
Saal, LH;Holm, K;Parsons, R
通讯作者：
Parsons, R