The content of cytokines in the blood of patients with various stages of breast cancer

Abstract

Background. Cytokine homeostasis is an important factor characterizing the general condition and adaptive capabilities of the body of patients with malignant neoplasms. However, the role of various growth factors and their significance in the development and enhancement of malignant growth in breast cancer remain poorly understood.

Aim. To evaluate the levels of cytokines - tumor necrosis factor α, interleukins-4, -6, -8 and -10 — in the blood serum of patients with different stages of breast cancer in comparison with healthy volunteers.

Material and methods. The study was conducted in 65 patients aged 25 to 67 years (mean age 44.5 [40.0–56.5] years). Two groups were distinguished: the first — with stage 1–2, the second — with stage 3–4 of breast cancer. The comparison group consisted of 15 apparently healthy women without cancer, aged 29 to 66 years (mean age 51.0 [39.0–61.0] years). Blood levels of tumor necrosis factor α, interleukins-4, -6, -8 and -10 were studied by enzyme immunoassay. The obtained data were processed using the methods of variation statistics, the Statistica 10.0 software package. The significance of differences was assessed by calculating the median and interquartile interval, analysis of variance was performed using the Kruskal–Wallis H-test, and Dan's Q-test was used for multiple comparisons. The critical significance level p for statistical tests was taken equal to 0.05.

Results. In the group of patients with stage 1–2 breast cancer, an increase in the blood levels of all studied cytokines was revealed in comparison with the group of healthy women: interleukin-6 (p=0.00719), interleukin-8 (p=0.00259), tumor necrosis factor α (p=0.00014), interleukin-4 (p1=0.0133), interleukin-10 (p1 <0.00001). In the group of patients with stage 3–4 breast cancer, an increase in blood levels was characteristic of all studied cytokines: interleukin-8 (p=0.00009), tumor necrosis factor α (p=0.000004), interleukin-4 (p <0.00001), interleukin-10 (p <0.00001), except for interleukin-6 (p=0.15608). The established patterns in changes in the content of cytokines in the blood of patients with breast cancer at different stages of development can serve as the basis for developing approaches to the diagnosis and treatment of the disease.

Conclusion. In patients with breast cancer, the levels of tumor necrosis factor α, interleukins-4, -6, -8, -10 (p <0.05) are higher than in healthy women.

Keywords

interleukin-4 / interleukin-6 / interleukin-8 / interleukin-10 / tumor necrosis factor α / breast cancer

References

[1] Zlokachestvennye novoobrazovaniya v Rossii 2019 godu (zabolevaemost' i smertnost'). (Malignant neoplasms in Russia in 2019 (morbidity and mortality).) Kaprin AD, Starinsky VV, Shakhzadova AO, editors. Moscow: MNIOI im PA Herzena — filial FGBU “NMIC radiologii” Minzdrava Rossii; 2020. 252 р. (In Russ.)

[2] Злокачественные новообразования в России в 2019 году (заболеваемость и смертность). Под ред. А.Д. Каприна, В.В. Старинского, А.О. Шахзадовой. М.: МНИОИ им. П.А. Герцена — филиал ФГБУ «НМИЦ радиологии» Минздрава России; 2020. 252 с.

[3] Stenina MB, Zhukova LG, Koroleva IA, Parokonnaya AA, Semiglazova TYu, Tyulyandin SA, Frolova MA. Practical recommendations for the drug treatment of invasive breast cancer. Russian Society of Clinical Oncology. Malignant tumors. 2019;9(3 S2):28–163. (In Russ.) DOI: 10.18027/2224-5057-2019-9-3s2-128-163.

[4] Стенина М.Б., Жукова Л.Г., Королева И.А., Пароконная А.А., Семиглазова Т.Ю., Тюляндин С.А., Фролова М.А. Практические рекомендации по лекарственному лечению инвазивного рака молочной железы. Российское общество клинической онкологии. Злокачественные опухоли. 2019;9(3 S2):28–163. DOI: 10.18027/2224-5057-2019-9-3s2-128-163.

[5] Serebrennikova SN, Seminsky IZh, Semenov NV, Guzovskaya EV. Interleukin-1, interleukin-10 in regulation of inflammatory process. Sibirskiy meditsinkiy zhurnal (Irkutsk). 2012;(8):5–7. (In Russ.)

[6] Серебренникова С.Н., Семинский И.Ж., Семенов Н.В., Гузовская Е.В. Интерлейкин-1, интерлейкин-10 в регуляции воспалительного процесса. Сибирский медицинский журнал (Иркутск). 2012;(8):5–7. EDN: PMSKVD.

[7] Tsybulkina NV, Tsybulkin NA. Mast cell as poly-functional element of immune system. Allergology and immunology in pediatrics. 2017;(2):4–11. (In Russ.)

[8] Цибулькина Н.В., Цибулькин Н.А. Тучная клетка как полифункциональный элемент иммунной системы. Аллергология и иммунология в педиатрии. 2017;(2):4–11.

[9] Ozhorbaev MT. The role of obesity in the course of breast cancer. Modern problems of science and education. 2021;(2):132. (In Russ.) DOI: 10.17513/spno.30627.

[10] Ожорбаев М.Т. Роль ожирения в течении рака молочной железы. Современные проблемы науки и образования. 2021;(2):132. DOI: 10.17513/spno.30627.

[11] Frolova MA, Glazkova EV, Stenina MB. Palbociclib in the first line combination hormone therapy of her2-negative metastatic hormone-dependent breast cancer. clinical follow-up. Medical council. 2018;(10):158–160. (In Russ.) DOI: 10.21518/2079-701X-2018-10-158-160.

[12] Фролова М.А., Глазкова Е.В., Стенина М.Б. Палбоциклиб в первой линии комбинированной терапии метастатического гормонозависимого HER-2 негативного рака молочной железы. Медицинский совет. 2018;(10):158–160. DOI: 10.21518/2079-701X-2018-10-158-160.

[13] Demidov SM, Demidov DA, Sazonov SV. Diagnosis and treatment of precancerous diseases of the breast. Monograph. Medicine. Pharmacology. Moscow; 2014. р. 25–89.(In Russ.)

[14] Демидов С.М., Демидов Д.А., Сазонов С.В. Диагностика и лечение предраковых заболеваний молочной железы. Монография. Медицина. Фармакология. М.; 2014. с. 25–89.

[15] Timerbulatov VM, Egorova NN. Results of the Department of medical Sciences of the Academy of Sciences of the Republic of Belarus for 2014. Monograph. Ufa: AN RB Gilem; 2015. р. 4–30. (In Russ.)

[16] Тимербулатов В.М., Егорова Н.Н. Итоги деятельности Отделения медицинских наук АН РБ за 2014 год. Монография. Уфа: АН РБ Гилем; 2015. с. 4–30.

[17] Gareev EM. Osnovy matematiko-statisticheskoy obrabotki mediko-biologicheskoy informatsii. (Fundamentals of mathematical and statistical processing of medical and biological information.) Ufa: Izd-vo GOU VPO “Bashgosmeduniversitet Rozdrava”; 2009. 346 р. (In Russ.)

[18] Гареев Е.М. Основы математико-статистической обработки медико-биологической информации. Уфа: Изд-во ГОУ ВПО �Башгосмедуниверситет Роздрава�; 2009. 346 с.

[19] Sheen-Chen SM, Chen WJ, Eng HL, Chou FF. Serum concentration of tumor necrosis factor in patients with breast cancer. Breast Cancer Res Treat. 1997;43(3):211–215. DOI: 10.1023/A:1005736712307.

[20] Hamed EA, Zakhary MM, Maximouset DW. Apoptosis, angiogenesis, inflammation, and oxidative stress: Basic interactions in patients with early and metastatic breast cancer. J Cancer Res Clin Oncol. 2012;138(6):999–1009. DOI: 10.1007/s00432-012-1176-4.

[21] Wolf JS, Chen Z, Dong G, Sunwoo JB, Bancroft CC, Capo DE, Yeh NT, Mukaida N, Van Waes C. IL (interleukin)-1 alpha promotes nuclear factor-kappa B and AP-1-induced IL-8 expression, cell survival, and proliferation in head and neck squamous cell carcinomas. Clin Cancer Res. 2001;7(6):1812–1820. PMID: 11410524.

[22] Yokoe T, Iino Y, Morishita Y. Trends of IL-6 and IL-8 levels in patients with recurrent breast cancer: preliminary report. Breast Cancer. 2000;7(3):187–190. DOI: 10.1007/BF02967458.

[23] Bachelot T, Ray-Coquard I, Menetrier-Caux C, Rastkha M, Duc A, Blay J-Y. Prognostic value of serum levels of interleukin 6 and of serum and plasma levels of vascular endothelial growth factor in hormone-refractory metastatic breast cancer patients. Br J Cancer. 2003;88(11):1721–1726. DOI: 10.1038/sj.bjc.6600956.

[24] Babyshkina NN, Dronova TA, Zambalova EA, Zavyalova MV, Slonimskaya EM, Cherdyntseva NV. The role of epidermal growth factor receptor (EGFR) in the efficacy of neoadjuvant chemotherapy in triple-negative breast cancer patients. Bulletin of Siberian Medicine. 2020;19(1):13–20. (In Russ.) DOI: 10.20538/1682-0363-2020-1-13-20.

[25] Бабышкина Н.Н., Дронова Т.А., Замбалова Е.А., Завьялова М.В., Слонимская Е.М., Чердынцева Н.В. Роль рецептора эпидермального фактора роста EGFR в эффективности неоадъювантной химиотерапии у больных тройным негативным раком молочной железы. Бюллетень сибирской медицины. 2020;19(1):13–20. DOI: 10.20538/1682-0363-2020-1-13-20.

[26] Kozłowski L, Zakrzewska I, Tokajuk P, Wojtukiewicz MZ. Concentration of interleukin-6 (IL-6), interleukin-8 (IL-8) and interleukin-10 (IL-10) in blood serum of breast cancer patients. Rocz Akad Med Bia1ymst. 2003;48:82–84. PMID: 14737948.

[27] Lykov AP, Kabakov AV, Bondarenko NA, Poveshchenko OV, Reiter TV, Kazakov OV, Strunkin DN, Poveshchenko AF, Orlov NB, Konenkov VI. Levels of hormones, microRNA and cytokines in lymph from healthy and experimental breast cancer. Siberian Journal of Oncology. 2016;15(5):33–39. (In Russ.) DOI: 10.21294/1814-4861-2016-15-5-33-39.

[28] Лыков А.П., Кабаков А.В., Бондаренко Н.А., Повещенко О.В., Райтер Т.В., Казаков О.В., Стрункин Д.Н., Повещенко А.Ф., Орлов Н.Б., Коненков В.И. Уровни гормонов, микроРНК и цитокинов в лимфе в норме и при раке молочной железы в эксперименте. Сибирский онкологический журнал. 2016;15(5):33–39. DOI: 10.21294/1814-4861-2016-15-5-33-39.

[29] Angelo LS, Kurzrock R. Vascular endothelial growth factor and its relationship to inflammatory mediators. Clin Cancer Res. 2007;13(10):2825–2830. DOI: 10.1158/1078-0432.CCR-06-2416.

RIGHTS & PERMISSIONS

Eco-Vector