Effect of Paclitaxel in Combination with Epirubicin Neoadjuvant Chemotherapy on Expression of CXCR4 in Breast Cancer and its Clinical Significance_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

CAI Wei , LIU Dandan , KANG Hua , HAI Tao , CUI Yeqing , SUN Haichen.

Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China;

Corresponding author：

Keywords：

Breast cancer; Neoadjuvant chemotherapy; CXCR4; Paclitaxel; Epirubicin

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Objective To evaluate the effect of neoadjuvant chemotherapy on the expression of CXCR4 in breast cancer and its clinical significance.
Methods The clinical data of 59 patients with breast cancer of stage Ⅱ and stage Ⅲ underwent neoadjuvant chemotherapy with paclitaxel plus epirubicin for 3 cycles between April 2005 and March 2009 were retrospectively analyzed. The expression of CXCR4 in the breast cancer tissues before and after neo-adjuvant chemotherapy was examined by immunohistochemistry and its relationship with clinicopathologic factors was analyzed.
Results The CXCR4 positive expression was observed in 56 patients with breast cancer (94.9%), but not in corresponding nontumor normal tissues. The expression level of CXCR4 was correlated to lymph nodes metastasis (P=0.019) and breast cancer stage (P=0.040), but it was not correlated to age of patients, tumor size, grade, hormone receptor (ER and PR)， and HER2 status. The expression level of CXCR4 was significantly decreased after neoadjuvant chemotherapy. Decline extent of CXCR4 expression after chemotherapy and CXCR4 expression level were not correlated to the effect of neoadjuvant chemotherapy, while the effect of chemotherapy in patients expressed CXCR4 in cluster distribution was better than that in scattering distribution (P=0.015). Conclusion The decline extent of CXCR4 expression level after paclitaxel combined with epirubicin neoadjuvant chemotherapy is not correlated to the efficacy, but its expressing distribution may be considered as an index to the effect of neoadjuvant chemotherapy.

Citation： CAI Wei,LIU Dandan,KANG Hua,HAI Tao,CUI Yeqing,SUN Haichen.. Effect of Paclitaxel in Combination with Epirubicin Neoadjuvant Chemotherapy on Expression of CXCR4 in Breast Cancer and its Clinical Significance. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2010, 17(8): 812-815下转823. doi: Copy

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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.
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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, 康骅, 海涛, 等. 基质细胞衍生因子1在乳腺癌肿瘤患者血浆中的表达及其临床意义 [J]. 中国普外基础与临床杂志, 2008; 15(12): 914916.
12. 康骅, Mansel RE, Jiang WG. 基质细胞衍化因子1的表达及其与乳腺癌患者预后的关系 [J]. 中国普外基础与临床杂志, 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. 黄桂林, 张剑权, 吴毅平, 等. 新辅助化疗对乳腺癌患者胰岛素样生长因子1受体表达的影响. [J]. 中国普外基础与临床杂志, 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.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Effect of Paclitaxel in Combination with Epirubicin Neoadjuvant Chemotherapy on Expression of CXCR4 in Breast Cancer and its Clinical Significance

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