ET方案新輔助化療對乳腺癌組織中CXCR4表達的影響及臨床意義_《中國普外基礎與臨床雜志》

作者：

蔡偉 , 劉丹丹 , 康驊 , 海濤 , 崔葉青 , 孫海晨

首都醫科大學宣武醫院普外科（北京 100053）;

關鍵詞：

乳腺癌新輔助化療 CXCR4 紫杉醇表阿霉素

視頻：

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目的探討ET方案新輔助化療對乳腺癌組織中CXCR4表達的影響及臨床意義。
方法回顧性分析我院2005年4月至2009年3月期間59例接受3周期ET（紫杉醇+表阿霉素）方案新輔助化療的Ⅱ期、Ⅲ期乳腺癌患者的臨床資料，應用免疫組化方法檢測乳腺癌組織中CXCR4的表達情況，分析其與臨床病理特征的關系。
結果 CXCR4在乳腺癌組織中的表達陽性率為94.9%（56/59），在癌旁正常組織中不表達。CXCR4表達水平與淋巴結轉移（P=0.019）及腫瘤TNM分期有關（P=0.040），與患者年齡、腫瘤大小、組織學分級、ER和PR狀態以及HER2表型無關（P gt;0.05）。新輔助化療后CXCR4表達水平下降，但CXCR4的表達水平及化療后下降的比例與化療療效無關（P gt;0.05）。CXCR4的表達分布狀態中呈簇狀分布者化療療效好于呈散在分布者（P =0.015）。
結論 ET方案新輔助化療后乳腺癌組織中CXCR4的表達水平下降比例與化療療效無關，但其表達的分布狀態可作為新輔助化療療效的參考指標。

引用本文： 蔡偉,劉丹丹,康驊,海濤,崔葉青,孫海晨. ET方案新輔助化療對乳腺癌組織中CXCR4表達的影響及臨床意義. 中國普外基礎與臨床雜志, 2010, 17(8): 812-815下轉823. doi: 復制

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11.	陶金波, 康驊, 海濤, 等. 基質細胞衍生因子1在乳腺癌腫瘤患者血漿中的表達及其臨床意義 [J]. 中國普外基礎與臨床雜志, 2008; 15(12): 914916.
12.	康驊, Mansel RE, Jiang WG. 基質細胞衍化因子1的表達及其與乳腺癌患者預后的關系 [J]. 中國普外基礎與臨床雜志, 2005; 12(5): 483487.
13.	Kang H, Watkins G, Parr C, et al. Stromal cell derived factor1: its influence on invasiveness and migration of breast cancer cells in vitro, and its association with prognosis and survival in human breast cancer [J]. Breast Cancer Res, 2005; 7(4): R402R410.
14.	Müller A, Homey B, Soto H, et al. Involvement of chemokine receptors in breast cancer metastasis [J]. Nature, 2001; 410(6824): 5056.
15.	Richert MM, Vaidya KS, Mills CN, et al. Inhibition of CXCR4 by CTCE9908 inhibits breast cancer metastasis to lung and bone [J]. Oncol Rep, 2009; 21(3): 761767.
16.	Mirisola V, Zuccarino A, Bachmeier BE, et al. CXCL12/SDF1 expression by breast cancers is an independent prognostic marker of diseasefree and overall survival [J]. Eur J Cancer, 2009; 45(14): 25792587.
17.	黃桂林, 張劍權, 吳毅平, 等. 新輔助化療對乳腺癌患者胰島素樣生長因子1受體表達的影響. [J]. 中國普外基礎與臨床雜志, 2009; 16(10): 834837.
18.	Fernandes RC, Bevilacqua JL, Soares IC, et al. Coordinated expression of ER, PR and HER2 define different prognostic subtypes among poorly differentiated breast carcinomas [J]. Histopathology, 2009; 55(3): 346352.
19.	Safwat MD, Habib F, Elayat A, et al. Morphometric and immunohistochemical study of angiogenic marker expressions in invasive ductal carcinoma of human breast [J]. Folia Morphol (Warsz), 2009; 68(3): 144155.
20.	Stroescu C, Dragnea A, Ivanov B, et al. Expression of p53, Bcl2, VEGF, Ki67 and PCNA and prognostic significance in hepatocellular carcinoma [J]. J Gastrointestin Liver Dis, 2008; 17(4): 411417.
21.	Jones RL, Salter J, A’Hern R, et al. The prognostic significance of Ki67 before and after neoadjuvant chemotherapy in breast cancer [J]. Breast Cancer Res Treat, 2009; 116(1): 5368.
22.	Lu DY, Tang CH, Yeh WL, et al. SDF1 upregulates interleukin6 through CXCR4, PI3K/Akt, ERK, and NFκBdependent pathway in microglia [J]. Eur J Pharmacol, 2009; 613(13): 146154.
23.	Yuan Y, Kan H, Fang Q, et al. CXCR4 receptor antagonist blocks cardiac myocyte p38 MAP kinase phosphorylation by HIV gp120 [J]. Cardiovasc Toxicol, 2008; 8(4): 173180.
24.	Sengupta N, Afzal A, Caballero S, et al. Paracrine modulation of CXCR4 by IGF1 and VEGF: implications for choroidal neovascularization [J]. Invest Ophthalmol Vis Sci, 2009; 51(5): 26972704.
25.	Robinson BD, Jones JG. Tumor microenvironment of metastasis (TMEM): a novel tissuebased assay for metastatic risk in breast cancer [J]. Future Oncol, 2009; 5(7): 919921.
26.	Sund M, Kalluri R. Tumor stroma derived biomarkers in cancer [J]. Cancer Metastasis Rev, 2009; 28(12): 177183.
27.	Xouri G, Christian S. Origin and function of tumor stroma fibroblasts [J]. Semin Cell Dev Biol, 2009; 21(1): 4046.

1. Specht J, Gralow JR. Neoadjuvant chemotherapy for locally advanced breast cancer [J]. Semin Radiat Oncol, 2009; 19(4): 222228.
2. Dowsett M, Procter M, McCaskillStevens W, et al. Diseasefree survival according to degree of HER2 amplification for patients treated with adjuvant chemotherapy with or without 1 year of trastuzumab: the HERA Trial [J]. J Clin Oncol, 2009; 27(18): 29622969.
3. Clavarezza M, Venturini M. Adjuvant chemotherapy for the treatment of HER2positive early breast cancer [J]. Oncology, 2009; 77 Suppl 1: 1417.
4. Kang H, Watkins G, DouglasJones A,et al. The elevated level of CXCR4 is correlated with nodal metastasis of human breast cancer [J]. Breast, 2005; 14(5): 360367.
5. Huang EH, Singh B, Cristofanilli M, et al. A CXCR4 antagonist CTCE9908 inhibits primary tumor growth and metastasis of breast cancer [J]. J Surg Res, 2009; 155(2): 231236.
6. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1) [J]. Eur J Cancer, 2009; 45(2): 228247.
7. Ogston KN, Miller ID, Payne S, et al. A new histological grading system to assess response of breast cancers to primary chemotherapy: prognostic significance and survival [J]. Breast, 2003; 12(5): 320327.
8. Mayr D, Heim S, Werhan C, et al. Comprehensive immunohistochemical analysis of Her2/neu oncoprotein overexpression in breast cancer: HercepTest (Dako) for manual testing and Her2/neuTest 4B5 (Ventana) for Ventana BenchMark automatic staining system with correlation to results of fluorescence in situ hybridization (FISH) [J]. Virchows Arch, 2009; 454(3): 241248.
9. Kato M, Kitayama J, Kazama S, et al. Expression pattern of CXC chemokine receptor4 is correlated with lymph node metastasis in human invasive ductal carcinoma [J]. Breast Cancer Res, 2003; 5(5): R144R150.
10. Wang CJ, Zhou ZG, Holmqvist A, et al. Survivin expression quantified by Image ProPlus compared with visual assessment [J]. Appl Immunohistochem Mol Morphol, 2009; 17(6): 530535.
11. 陶金波, 康驊, 海濤, 等. 基質細胞衍生因子1在乳腺癌腫瘤患者血漿中的表達及其臨床意義 [J]. 中國普外基礎與臨床雜志, 2008; 15(12): 914916.
12. 康驊, Mansel RE, Jiang WG. 基質細胞衍化因子1的表達及其與乳腺癌患者預后的關系 [J]. 中國普外基礎與臨床雜志, 2005; 12(5): 483487.
13. Kang H, Watkins G, Parr C, et al. Stromal cell derived factor1: its influence on invasiveness and migration of breast cancer cells in vitro, and its association with prognosis and survival in human breast cancer [J]. Breast Cancer Res, 2005; 7(4): R402R410.
14. Müller A, Homey B, Soto H, et al. Involvement of chemokine receptors in breast cancer metastasis [J]. Nature, 2001; 410(6824): 5056.
15. Richert MM, Vaidya KS, Mills CN, et al. Inhibition of CXCR4 by CTCE9908 inhibits breast cancer metastasis to lung and bone [J]. Oncol Rep, 2009; 21(3): 761767.
16. Mirisola V, Zuccarino A, Bachmeier BE, et al. CXCL12/SDF1 expression by breast cancers is an independent prognostic marker of diseasefree and overall survival [J]. Eur J Cancer, 2009; 45(14): 25792587.
17. 黃桂林, 張劍權, 吳毅平, 等. 新輔助化療對乳腺癌患者胰島素樣生長因子1受體表達的影響. [J]. 中國普外基礎與臨床雜志, 2009; 16(10): 834837.
18. Fernandes RC, Bevilacqua JL, Soares IC, et al. Coordinated expression of ER, PR and HER2 define different prognostic subtypes among poorly differentiated breast carcinomas [J]. Histopathology, 2009; 55(3): 346352.
19. Safwat MD, Habib F, Elayat A, et al. Morphometric and immunohistochemical study of angiogenic marker expressions in invasive ductal carcinoma of human breast [J]. Folia Morphol (Warsz), 2009; 68(3): 144155.
20. Stroescu C, Dragnea A, Ivanov B, et al. Expression of p53, Bcl2, VEGF, Ki67 and PCNA and prognostic significance in hepatocellular carcinoma [J]. J Gastrointestin Liver Dis, 2008; 17(4): 411417.
21. Jones RL, Salter J, A’Hern R, et al. The prognostic significance of Ki67 before and after neoadjuvant chemotherapy in breast cancer [J]. Breast Cancer Res Treat, 2009; 116(1): 5368.
22. Lu DY, Tang CH, Yeh WL, et al. SDF1 upregulates interleukin6 through CXCR4, PI3K/Akt, ERK, and NFκBdependent pathway in microglia [J]. Eur J Pharmacol, 2009; 613(13): 146154.
23. Yuan Y, Kan H, Fang Q, et al. CXCR4 receptor antagonist blocks cardiac myocyte p38 MAP kinase phosphorylation by HIV gp120 [J]. Cardiovasc Toxicol, 2008; 8(4): 173180.
24. Sengupta N, Afzal A, Caballero S, et al. Paracrine modulation of CXCR4 by IGF1 and VEGF: implications for choroidal neovascularization [J]. Invest Ophthalmol Vis Sci, 2009; 51(5): 26972704.
25. Robinson BD, Jones JG. Tumor microenvironment of metastasis (TMEM): a novel tissuebased assay for metastatic risk in breast cancer [J]. Future Oncol, 2009; 5(7): 919921.
26. Sund M, Kalluri R. Tumor stroma derived biomarkers in cancer [J]. Cancer Metastasis Rev, 2009; 28(12): 177183.
27. Xouri G, Christian S. Origin and function of tumor stroma fibroblasts [J]. Semin Cell Dev Biol, 2009; 21(1): 4046.

《中國普外基礎與臨床雜志》

ET方案新輔助化療對乳腺癌組織中CXCR4表達的影響及臨床意義

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《中國普外基礎與臨床雜志》

ET方案新輔助化療對乳腺癌組織中CXCR4表達的影響及臨床意義

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

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