Abstract
Background
We reported that IL-6 and IL-8 levels at the beginning of treatment are predictive indicators of response to therapy and prognosis of patients with recurrent breast cancer. The aim of this study was to investigate the trend of IL-6 and IL-8 levels in heavily pretreated patients with recurrent breast cancer.
Methods
Cytokine level trends in 12 patients heavily pretreated with anthracyclines were studied. Patients were divided into two groups according to the objective response. There were 5 partial response (PR)/no change (NC), and 7 progressive disease (PD) patients. Blood was taken every four weeks. IL-6 was measured by chemiluminescent enzyme immunoassay. IL-8 was measured by ELISA.
Results
The pretreatment level of IL-6 in the PR/NC group (11.0±2.1 pg/ml) was significantly lower than that (15.3±2.7 pg/ml) in the PD group. However, there was no difference in IL-8 level between the PR/NC group (12.5±5.5 pg/ml) and the PD group (11.5±1.1 pg/ml). IL-6 levels in the PR/NC group were maintained within normal levels or decreased to within normal levels after treatment, while levels of IL-6 in the PD group gradually increased until the time of patient death. A decrease in IL-8 level after treatment was observed in only one patient in the PR/NC group. Mild increase of IL-8 levels was observed in the PD group.
Conclusion
Continuous elevation of IL-6 levels indicates poor prognosis in heavily pretreated patients with recurrent breast cancer. Combination therapy including agents that reduce IL-6 levels will be a new strategy for aggressively treating recurrent breast cancer.
Similar content being viewed by others
Abbreviations
- IL:
-
Interleukin
- TNF:
-
Tumor necrosis factor
- PR:
-
Partial response
- NC:
-
No change
- PD:
-
Progressive disease
- ELISA:
-
Enzyme-linked immunosorbent assay
- SEM:
-
Standard error of the mean
- MPA:
-
Medroxyprogesterone acetate
- 5′DFUR:
-
Doxifluridine
References
Kushner I: The acute phase response: An overview.Methods Enzymol 163:373–383, 1988.
Hirano T, Yasukawa K, Harada H,et al: Complementary DNA for a novel human interleukin (BSF-s) that induces B lymphocytes to produce immunoglobulin.Nature 324:73–76, 1986.
Kishimoto T: The biology of interleukin-6.Blood 74:1–10, 1989.
Detmers PA, Lo SK, Olsen-Egbert E,et al: Neutrophil-activated protein 1/interleukin-8 stimulates the binding activity of the leukocyte adhesion receptor CDllb/CD18 on human neutrophils.J Exp Med 171:1155–1162, 1990.
Huber AR, Kunkel SL, Todd RF,et al: Regulation of transendothelial neutrophil migration by endogenous interleukin-8.Science 254:99–102, 1991.
Strassman G, Fong M, Kenney JS,et al: Evidence for the involvement of interleukin 6 in experimental cancer cachexia.J Clin Invest 89:1681–1684, 1992.
Yasumoto K, Mukaida N, Harada A,et al: Molecular analysis of the cytokine network involved in cachexia in colon 26 adenocarcinoma-bearing mice.Cancer Res 55:921–927, 1995.
Kajimura N, Iseki H, Tanaka R,et al: Toxohormones responsible for cancer cachexia syndrome in nude mice bearing human cancer cell lines.Cancer Chemother Pharmacol 38:48–52, 1996.
Bobus VJ, Moll R, Gerharz DG,et al: Differential characteristics of two new tumorigenic cell lines of human breast carcinoma origin.Int J Cancer 77:415–423, 1998.
Kurebayashi J, Otsuki T, Tang CK,et al: Isolation and characterization of a new human breast cancer cell line, KPL-4, expressing the Erb B family receptors and interleukin-6.Br J Cancer 79:707–717, 1999.
Yokoe T, Lino Y, Takei H,et al: Changes of cytokines and thyroid function in patients with recurrent breast cancer.Anticancer Res 17:695–700, 1997.
Zhan GJ, Adachi I: Serum interleukin-6 levels correlate to tumor progression and prognosis in metastatic breast cancer.Anticancer Res 19 (2B): 1427–1432, 1999.
Reiter Z, Chen L, Revel M,et al: Interleukin-6 protects ductal breast carcinoma cells from MHC-unrestricted cell-mediated cytotoxicity.Lymphokine Cytokine Res 11:175–181, 1992.
Reed MJ, Topping L, Goldham NG,et al: Control of aromatase activity in breast cancer cells: The roll of cytokines and growth factors.J Steroid Biochem Molec Biol 44:589–596, 1993.
Purohit A, Ghilchik MW, Duncan L,et al: Aromatase activity and interleukin-6 production by normal and malignant tissues.J Clin Endocrinol Metab 80:3052–3058, 1995.
Asgeirsson KS, Olafsdottir K, Jonasson JG,et al: The effects of IL-6 on cell adhesion and e-cadherin expression in breast cancer.Cytokine 10:720–728, 1998.
Kishimoto T, Akira S, Taga T: IL-6 receptor and mechanism of signal transduction.Int J Immunopharmacol 14:431–438, 1992.
Kishimoto T: Interleukin-6 and its receptor in autoimmunity.J Autoimmun 5 Suppl A:123–132, 1992.
Haverty AA, Harmey JH, Redmond HP,et al: Interleukin-6 upregulates GP96 expression in breast cancer.J Surg Res 69:145–149, 1997.
Yokoe T, Lino Y, Takei H,et al: Relationship between thyroid-pituitary function and response to therapy in patients with recurrent breast cancer.Anticancer Res 16:2069–2072, 1996.
Pittman CS, Suda AK, Chambers JB,et al: Abnormalities of thyroid hormone turnover in patients with diabetes mellitus before and after insulin therapy.J Clin Endocrinol Metab 48:854–860, 1979.
Wiersinga WM, Lie KI, Touber JL: Thyroid hormones in acute myocardial infarction.Clin Endoclinol 14:367–374, 1981.
Lim VS, Fang VS, Kats AI,et al: Thyroid dysfunction in chronic renal failure.J Clin Invest 60:522–534, 1977.
Nomura S, Pittman CS, Chambers JB,et al: Reduced peripheral conversion of thyroxin to triiodothyronine in patients with hepatic cirrhosis.J Clin Invest 56:643–652, 1975.
Davidson SB, Dulchafsky SA, Diebel LN,et al: Effect of sepsis and 3,5,3’-triiodothyronine replacement on myocardial integrity during oxidant challenge.Crit Care Med 24:850–854, 1996.
Walker JD, Crawford FA, Mukherjee R,et al: Direct effect of acute administration of 3,5,3’-triiodo-L-thyronine on myocyte function.Ann Thorac Surg 58:851–856, 1994.
Morkin E, Pennock GD, Raya TE,et al: Studies on the use of thyroid hormone and a thyroid hormone analogue in the treatment of congestive heart failure.Ann Thorac Surg 56:S54–60, 1993.
Dulchafsky SA, Kenzenko SM, Saba AA,et al: Triiodothyronine (T3) supplementation maintains surfactant biochemical integrity during sepsis.J Trauma 39:53–58, 1995.
Yamashita J, Hideshima T, Shirakusa T,et al: Medroxyprogesterone acetate treatment reduces serum interleukin-6 levels in patients with metastatic breast carcinoma.Cancer 78:2346–2352, 1996.
Kurebayashi J, Yamamoto S, Otsuki T,et al: Medroxyprogesterone acetate inhibits interleukin 6 secretion from KPL-4 human breast cancer cells bothin vitro andin vivo; A possible mechanism of the anticachectic effect.Br J Cancer 79:631–636, 1999.
Yokoe T, Iino Y, Sugamata N,et al: Phase II trial of mitoxantrone, doxifluridine and medroxyprogesterone acetate as second-line treatment for anthracycline-resistant metastatic breast cancer.Anticancer Res 15:2303–2306, 1995.
Iino Y, Yokoe T, Sugamata N,et al: A combination chemoendocrine therapy of mitoxantrone, doxifluridine, and medroxyprogesterone acetate for anthracycline-resistant advanced breast cancer.Cancer Chemother Pharmacol 41:243–247, 1998.
Purohit A, Singh A, Ghilchik MW,et al: Inhibition of tumor necrosis factor alpha-stimulated aromatase activity by microtubule-stabilizing agents, paclitaxel and 2-methoxyestradiol.Biochem Biophys Res Commun 261:214–217, 1999.
Sawada N, Ishikawa T, Fukase Y,et al: Induction of thymidine phosphorylase activity and enhancement of capecitabine efficacy by taxol/taxotere in human cancer xenografts.Clin Cancer Res 4:1013–1019, 1998.
Author information
Authors and Affiliations
About this article
Cite this article
Yokoe, T., lino, Y. & Morishita, Y. Trends of IL-6 and IL-8 levels in patients with recurrent breast cancer: preliminary report. Breast Cancer 7, 187–190 (2000). https://doi.org/10.1007/BF02967458
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02967458