ABCR  Vol.3 No.3 , July 2014
Serum CK18 as a Predictive Factor of Response to Chemotherapy in Locally Advanced and Metastatic Breast Cancer
ABSTRACT

Introduction: Breast cancer is the most common cancer in women and the second most frequent cause of cancer death. Several factors affect response to chemotherapy including nodal status, hormonal status and human epidermal growth factor receptor (Her-2). Aim of Study: The study is aiming at evaluating M30 antigen in serum of patients with locally advanced and metastatic breast cancer and establishing the relation between M30 level and response to chemotherapy. Patients and Methods: The study was performed at Al Bairouni University Hospital and the Faculty of Pharmacy (Damascus-Syria). We have included 60 patients with histologic confirmation of invasive ductal carcinoma of the breast treated with the combination (Docetaxel + Doxorubicin) with M30 levels to be evaluated before treatment and 24 hours after the first and third cycle. Results: M30 level increase in serum 24 hours after the 1st cycle correlated with different kinds of response in 39 patients (P value less than 0.03) with better results in those with Estrogen Receptors (ER) positive patients (P value 0.05). There was no correlation between Her-2 status and response (P value 0.3). Conclusion: M30 level in serum is a useful predictor marker of response to chemotherapy in both locally advanced and metastatic breast cancer.


Cite this paper
Battah, B. , Saleh, J. , Bachour, M. and Salamoon, M. (2014) Serum CK18 as a Predictive Factor of Response to Chemotherapy in Locally Advanced and Metastatic Breast Cancer. Advances in Breast Cancer Research, 3, 79-83. doi: 10.4236/abcr.2014.33011.
References
[1]   Burstein, H.J. and Monica, M. (2008) Malignant Tumors of the Breast. In: Devita, V.T., Lawrence, T.S. and Rosenberg, S.A., Eds., Cancer Principles & Practice of Oncology, Vol. 2, Williams and Wilkins, Wolters Kluwer Lippincott, 1606-1654.

[2]   Shahla, M. (2000) Assessment of Prognostic Factors in Breast Fine-Needle Aspirates. American Journal of Clinical Pathology, 113, S84-S96.

[3]   Andrew, G. and Charles, S. (2000) Integrin-Mediated Survival Signals Regulate the Apoptotic Functions of Bax through Its Conformation and Subcellular Localization. The Journal of Cell Biology, 149, 431-445. http://dx.doi.org/10.1083/jcb.149.2.431

[4]   Lipponen, P. and Aaltomaa, S. (1994) Apoptosis in Bladder Cancer as Related To Standard Prognostic Factors and Prognosis. The Journal of Pathology, 173, 333-339.
http://dx.doi.org/10.1002/path.1711730408

[5]   Stennicke, H.R. and Salvesen, G.S. (1998) Properties of the Caspases. Biochimica et Biophysica Acta, 1387, 17-31. http://dx.doi.org/10.1016/S0167-4838(98)00133-2

[6]   Thornberry, N.A. and Lazebnik, Y. (1998) Caspases: Enemies within. Science (Wash. DC), 281, 1312-1316. http://dx.doi.org/10.1126/science.281.5381.1312

[7]   Keane, M.M., Ettenberg, S.A., Nau, M.M., et al. (1999) Chemotherapy Augments TRAIL-Induced Apoptosis in Breast Cell Lines. Cancer Research, 59, 734-741.

[8]   Bellarosa, D., Ciucci, A., Bullo, A., Nardelli, F., et al. (2001) Apoptotic Events in a Human Ovarian Cancer Cell Line Exposed to Anthracyclines. Journal of Pharmacology and Experimental Therapeutics, 296, 276-283.

[9]   Kottke, T.J., Blajeski, A.L., Martins, M.L., Mesner, P.W., et al. (1999) Comparison of Paclitaxel-, 5-fluoro-2-Deoxyuridine-, and Epidermal Growth Factor (EGF)-Induced Apoptosis. The Journal of Biological Chemistry, 274, 15927-15936. http://dx.doi.org/10.1074/jbc.274.22.15927

[10]   Suzuki, A., Kawabata, T. and Kato, M. (1998) Necessity of Interleukin-1β Converting Enzyme Cascade in Taxotere-Initiated Death Signaling. European Journal of Pharmacology, 343, 87-92.
http://dx.doi.org/10.1016/S0014-2999(97)01520-3

[11]   Linder, S. (2007) Cytokeratin Markers Come of Age. Tumor Biology, 28, 189-195.
http://dx.doi.org/10.1159/000107582

[12]   Ueno, T., Toi, M. and Linder, S. (2005) Detection of Epithelial Cell Death in the Body by Cytokeratin 18 Measurement. Biomed Pharmacother, 59, S359-S362. http://dx.doi.org/10.1016/S0753-3322(05)80078-2

[13]   Leers, M.P., Kolgen, W., Bjorklund, V., Bergman, T., et al. (1999) Immunocytochemical Detection and Mapping of a Cytokeratin 18 Neoepitope Exposed during Early Apoptosis. The Journal of Pathology, 187, 567-572.

[14]   de Haas, E.C., di Pietro, A., Simpson, K.L., Meijer, C., et al. (2008) Clinical Evaluation of M30 and M65 ELISA Cell Death Assays as Circulating Biomarkers in a Drug-Sensitive Tumor, Testicular Cancer. Neoplasia, 10, 1041-1048.

[15]   Wu, Y.X., Wang, J.H., Wang, H. and Yang, X.Y. (2003) Study on Expression of Ki-67, Early Apoptotic Protein M30 in Endometrial Carcinoma and Their Correlation with Prognosis. Zhonghua Bing Li Xue Za Zhi, 32, 314-318.

[16]   Yaman, E., Coskun, U., Sancak, B., Buyukberber, S., Ozturk, B. and Benekli, M. (2010) Serum M30 Levels Are Associated with Survival in Advanced Gastric Carcinoma Patients. International Immunopharmacology, 10, 719-722. http://dx.doi.org/10.1016/j.intimp.2010.03.013

[17]   Scholl, S.M., Beuzeboc, P., Harris, A.L., Pierga, J.Y., Asselain, B., Palangié, T., et al. (1998) Is Primary Chemotherapy Useful for All Patients with Primary Invasive Breast Cancer? Recent Results in Cancer Research, 152, 217-226. http://dx.doi.org/10.1007/978-3-642-45769-2_21

[18]   Holdenrieder, S. and Stieber, P. (2004) Apoptotic Markers in Cancer. Clinical Biochemistry, 37, 605-617. http://dx.doi.org/10.1016/j.clinbiochem.2004.05.003

[19]   Degterev, A. and Yuan, J. (2008) Expansion and Evolution of Cell Death Programmes. Nature Reviews Molecular Cell Biology, 9, 378-390. http://dx.doi.org/10.1038/nrm2393

[20]   Olofsson, M.H., Ueno, T., Pan, Y., Xu, R., Cai, F., van der Kuip, H., et al. (2007) Cytokeratin-18 Is a Useful Serum Biomarker for Early Determination of Response of Breast Carcinomas to Chemotherapy. Clinical Cancer Research, 13, 3198-3206. http://dx.doi.org/10.1158/1078-0432.CCR-07-0009

[21]   Meyn, R.E., Stephens, L.C., Hunter, N.R. and Milas, L. (1995) Apoptosis in Murine Tumors Treated with Chemotherapy Agents. Anti-Cancer Drugs, 6, 443-450. http://dx.doi.org/10.1097/00001813-199506000-00013

[22]   Ellis, P.A., Smith, I.E., McCarthy, K., Detre, S., Salter, J. and Dowsett, M. (1997) Preoperative Chemotherapy Induces Apoptosis in Early Breast Cancer. The Lancet, 349, 849.
http://dx.doi.org/10.1016/S0140-6736(05)61752-7

[23]   Green, A.M. and Steinmetz, N.D. (2002) Monitoring Apoptosis in Real Time. Cancer Journal, 8, 82-92. http://dx.doi.org/10.1097/00130404-200203000-00002

[24]   Morse, D.L., Gray, H., Payne, C.M. and Gillies, R.J. (2005) Docetaxel Induces Cell Death through Mitotic Catastrophe in Human Breast Cancer Cells. Molecular Cancer Therapeutics, 4, 1495-1504.
http://dx.doi.org/10.1158/1535-7163.MCT-05-0130

[25]   Jordan, M.A., Wendell, K., Gardiner, S., Derry, W.B., Copp, H. and Wilson, L. (1996) Mitotic Block Induced in HeLa Cells by Low Concentrations of Paclitaxel (Taxol) Results in Abnormal Mitotic Exit and Apoptotic Cell Death. Cancer Research, 56, 816-825.

[26]   Blajeski, A.L., Kottke, T.J. and Kaufmann, S.H. (2001) A Multistep Model for Paclitaxel-Induced Apoptosis in Human Breast Cancer Cell Lines. Experimental Cell Research, 270, 277-288.
http://dx.doi.org/10.1158/1535-7163.MCT-05-0130

 
 
Top