Serum thymidine kinase 1 levels predict cancer‑free survival following neoadjuvant, surgical and adjuvant treatment of patients with locally advanced breast cancer

Chen,Feiyu; Tang,Lili; Xia,Ting; He,Ellen; Hu,Guozhu; Li,Yuan; Zhang,Ming; Zhou,Ji; Eriksson,Staffan; Skog,Sven

doi:10.3892/mco.2013.149

Serum thymidine kinase 1 levels predict cancer‑free survival following neoadjuvant, surgical and adjuvant treatment of patients with locally advanced breast cancer

Authors:
- Feiyu Chen
- Lili Tang
- Ting Xia
- Ellen He
- Guozhu Hu
- Yuan Li
- Ming Zhang
- Ji Zhou
- Staffan Eriksson
- Sven Skog
View Affiliations

Affiliations: Department of Breast Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China, Department of Breast Oncology, The Second Affiliated Hospital of Guangzhou Medical College, Guangzhou, Guangdong, P.R. China, Sino‑Swedish Molecular Bio‑Medicine Research Institute, Shenzhen, Guangdong, P.R. China, Institute of Clinical Medicine, Jiangxi Provincial People's Hospital, Nanchang, Jiangxi, P.R. China, Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, Uppsala, Uppland, Sweden
Published online on: July 19, 2013 https://doi.org/10.3892/mco.2013.149
Pages: 894-902

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

In this study, the use of serum thymidine kinase 1 protein (STK1p) concentration for the prognosis of the overall survival of patients with locally advanced breast cancer (n=51) following routine treatment (neoadjuvant treatment, surgery and chemotherapy) was investigated. The patients were followed up for 44 months and the STK1p values were determined by a high‑sensitivity enhanced chemiluminescence (ECL) dot blot assay. The variables investigated in relation to metastasis and survival were STK1p, clinical stage, tumor size and age, by the Kaplan‑Meier method, the log‑rank test and Cox uni‑ and multivariate analyses. Patients with high STK1p values (≥2.0 pM) 3‑6 months after surgery exhibited a positive correlation to clinical stage, tumor size, occurrence of metastasis and survival. The hazard risk for the development of metastatic disease and mortality among breast cancer patients was 11‑12 times higher in patients with high compared to those with low STK1p values (<2.0 pM). Notably, patients with stage III̸IV disease and low STK1p values exhibited statistically significantly improved survival compared to patients with high STK1p values. A multivariate Cox analysis demonstrated that the STK1p levels 6 months after surgery was the only independent prognostic factor for metastasis and survival. In conclusion, STK1p is a prognostic marker in patients with locally advanced breast cancer and it may help identify a subgroup of stage III̸IV patients with improved cancer‑free survival expectancy, enabling personalized treatment.

View Figures

View References

1	Fisher B, Bryant J, Wolmark N, et al: Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol. 16:2672–2685. 1998.PubMed/NCBI
2	Scholl SM, Pierga JY, Asselain B, et al: Breast tumor response to primary chemotherapy predicts local and distant control as well as survival. Eur J Cancer. 31A:1969–1975. 1995. View Article : Google Scholar : PubMed/NCBI
3	Semiglazov VF, Topuzov EE, Bavli JL, et al: Primary (neoadjuvant) chemotherapy and radiotherapy compared with primary radiotherapy alone in stage IIb–IIIa breast cancer. Ann Ocol. 5:591–595. 1994.
4	Makris A, Powles TJ, Dowsett M, et al: Prediction of response to neoadjuvant chemoendocrine therapy in primary breast carcinomas. Clin Cancer Res. 3:593–600. 1997.PubMed/NCBI
5	Mauriac L, MacGrogan G, Avril A, et al: Neoadjuvant chemotherapy for operable breast carcinoma larger than 3 cm: a unicentre randomized trial with a 124-month median follow-up. Institute Bergonié Bordeaux Groupe Sein (IBBGS). Ann Oncol. 10:47–52. 1999. View Article : Google Scholar : PubMed/NCBI
6	van der Hage JA, van de Velde CJ, Julien JP, et al: Preoperative chemotherapy in primary operable breast cancer: results from the European Organization for Research and Treatment of Cancer trial 10902. J Clin Oncol. 19:4224–4237. 2001.
7	Fisher B, Gunduz N and Saffer EA: Influence of the interval between primary tumor removal and chemotherapy on kinetics and growth of metastases. Cancer Res. 43:1488–1492. 1983.PubMed/NCBI
8	Zhou J, He E and Skog S: The proliferation marker thymidine kinase 1 in clinical use (Review). Mol Clin Oncol. 1:18–28. 2013.
9	Sherley JL and Kelly TJ: Regulation of human thymidine kinase during the cell cycle. J Biol Chem. 263:8350–8358. 1988.PubMed/NCBI
10	Gasparri F, Wang N, Skog S, Galvani A and Eriksson S: Thymidine kinase 1 expression defines an activated G1 stage of the cell cycle as revealed with site-specific antibodies and ArrayScan assays. Eur J Cell Biol. 88:779–785. 2009. View Article : Google Scholar : PubMed/NCBI
11	NCCN Clinical Practice Guidelines in Oncology™. Breast Cancer V.2.2007. Available at: http://www.nccn.org. Accessed May 15, 2007
12	Goldstraw P and Groome P: Lung. International Union Against Cancer (UICC). TNM Classification of Malignant Tumours. Sobin LH, Gospodarowicz MK and Wittekind CH: 7th edition. Wiley-Blackwell; New York, NY: pp. 138–146. 2009
13	Wu C, Yang R, Zhou J, et al: Production and characterisation of a novel chicken IgY antibody raised against C-terminal peptide from human thymidine kinase 1. J Immunol Methods. 277:157–169. 2003. View Article : Google Scholar : PubMed/NCBI
14	He E, Xu XH, Guan H, et al: Thymidine kinase 1 is a potential marker for prognosis and monitoring the response to treatment of patients with breast, lung and esophageal cancer and non-Hodgkin’s lymphoma. Nucleosides Nucleotides Nucleic Acids. 29:352–358. 2010.PubMed/NCBI
15	Coskun U, Yamac D, Gulbahar O, et al: Locally advanced breast carcinoma treated with neoadjuvant chemotherapy: are the changes in serum levels of YKL-40, MMP-2 and MMP-9 correlated with tumor response? Neoplasma. 54:348–352. 2007.PubMed/NCBI
16	Martinez-Trufero J, de Lobera AR, Lao J, et al: Serum markers and prognosis in locally advanced breast cancer. Tumori. 91:522–530. 2005.PubMed/NCBI
17	Kinsella MD, Nassar A, Siddiqui MT and Cohen C: Estrogen receptor (ER), progesterone receptor (PR), and HER2 expression pre- and post- neoadjuvant chemotherapy in primary breast carcinoma: a single institutional experience. Int J Clin Exp Pathol. 5:530–536. 2012.
18	Lee JS, Son BH and Ahn SH: The predictive value of serum HER2/neu for response to anthracycline-based and trastuzumab-based neoadjuvant chemotherapy. J Breast Cancer. 15:189–196. 2012. View Article : Google Scholar : PubMed/NCBI
19	Mazouni C, Hall A, Broglio K, et al: Kinetics of serum HER-2/neu changes in patients with HER-2-positive primary breast cancer after initiation of primary chemotherapy. Cancer. 109:496–501. 2007. View Article : Google Scholar : PubMed/NCBI
20	Leyland-Jones B and Smith BR: Serum HER2 testing in patients with HER2-positive breast cancer: the death knell tolls. Lancet Oncol. 12:286–295. 2011. View Article : Google Scholar : PubMed/NCBI
21	Holm NT, Byrnes K, Li BD, et al: Elevated levels of chemokine receptor CXCR4 in HER-2 negative breast cancer specimens predict recurrence. J Surg Res. 141:53–59. 2007. View Article : Google Scholar : PubMed/NCBI
22	Chen F and Tang L: Significance of S-TK1 detecting in breast cancer patients and its relationship with prognosis. Can Res Prev Treat. 39:637–641. 2012.(In Chinese).
23	Liedtke C, Mazouni C, Hess KR, et al: Response to neoadjuvant therapy and long-term survival with triple-negative breast cancer. J Clin Oncol. 26:1275–1281. 2008. View Article : Google Scholar : PubMed/NCBI
24	Onitilo AA, Engel JM, Greenlee RT and Mukesh BN: Breast cancer subtypes based on ER/PR and Her2 expression: comparison of clinicopathologic features and survival. Clin Med Res. 7:4–13. 2009. View Article : Google Scholar : PubMed/NCBI
25	Verma S, Provencher L and Dent R: Emerging trends in the treatment of triple-negative breast cancer in Canada: a survey. Curr Oncol. 18:180–190. 2011. View Article : Google Scholar : PubMed/NCBI
26	Pinhel I, Hills M, Drury S, et al: ER and HER2 expression are positively correlated in HER2 non-overexpressing breast cancer. Breast Cancer Res. 14:R462012. View Article : Google Scholar : PubMed/NCBI
27	He Q, Fornander T, Johansson H, et al: Thymidine kinase 1 in serum predicts increased risk of distant or loco-regional recurrence following surgery in patients with early breast cancer. Anticancer Res. 26:4753–4759. 2006.PubMed/NCBI
28	Xu Y, Shi QL, Ma H, et al: High thymidine kinase 1 (TK1) expression is a predictor of poor survival in patients with pT1 of lung adenocarcinoma. Tumour Biol. 33:475–483. 2012. View Article : Google Scholar : PubMed/NCBI
29	Chen G, He C, Li L, et al: Nuclear TK1 expression is an independent prognostic factor for survival in pre-malignant and malignant lesions of the cervix. BMC Cancer. 13:249–258. 2013. View Article : Google Scholar : PubMed/NCBI
30	Nisman B, Allweis T, Kadouri L, et al: Comparison of diagnostic and prognostic performance of two assays measuring thymidine kinase 1 activity in serum of breast cancer patients. Clin Chem Lab Med. 51:439–447. 2013. View Article : Google Scholar : PubMed/NCBI
31	He Q, Zou L, Zhang PA, et al: The clinical significance of thymidine kinase 1 measurement in serum of breast cancer patients using anti-TK1 antibody. Int J Biol Markers. 15:139–146. 2000.PubMed/NCBI
32	Chen ZH, Huang SQ, Wang Y, et al: Serological thymidine kinase 1 is a biomarker for early detection of tumours - a health screening study on 35,365 people, using a sensitive chemiluminescent dot blot assay. Sensors (Basel). 11:11064–11080. 2011. View Article : Google Scholar : PubMed/NCBI