Tumor Biology

, Volume 36, Issue 2, pp 815–822 | Cite as

Clinical utility of certain biomarkers as predictors of breast cancer with or without metastasis among Egyptian females

  • Samia A. Ahmed
  • Manal A. Hamed
  • Omar S. Omar
Research Article


The objective of this study is to explore and correlate the value of certain biomarkers in breast cancer (BC) females with and without metastasis after undergoing the surgical treatment protocol in the National Cancer Institute in Egypt. Thirty females (33–69 years), diagnosed as early breast cancer patients with or without metastasis, and 20 healthy individuals were selected for this study. The biomarkers under investigation were vascular endothelial growth factor (VEGF), C-reactive protein (CRP), interleukin-6 (IL-6), and interleukin-8 (IL-8). The correlation between these markers and the tumor grade was also evaluated. The results revealed a significant increase (p < 0.0001) in VEGF, CRP, IL-6, and IL-8 in breast cancer patients with or without metastasis as compared to the healthy group. Surgical treatment of metastatic BC females showed a significant reduction of those parameters by variable degrees, whereas BC females without metastasis recorded the most inhibition levels. Also, there was positive correlation (p < 0.0001) between those biomarkers and the tumor grades. We also noticed an association between VEGF and IL-8 as well as CRP and IL-6. In conclusion, the selected biomarkers may be beneficial for the prognosis of breast cancer and seem to be a diagnostic tool to differentiate between BC with or without metastasis. The descried surgical treatment protocol succeeded to attenuate the elevated biomarker levels and improve patient survival which deserves more extensive studies.


Breast cancer VEGF CRP IL-6 IL-8 Metastasis 


Conflicts of interest



  1. 1.
    Taha FM, Zeeneldin AA, Helal AM, Gaber AA, Sallam YA, Ramadan H, et al. Prognostic value of serum vascular endothelial growth factor in Egyptian females with metastatic triple negative breast cancer. Clin Biochem. 2009;42:1420–6.CrossRefPubMedGoogle Scholar
  2. 2.
    Coelho BA, Vilac A, Belo B, Andrade SP, Amorim WA, Uemura G, et al. N-Acetylglucosaminidase, myeloperoxidase and vascular endothelial growth factor serum levels in breast cancer patients. Biomed Pharmacother. 2014;68:185–9.CrossRefPubMedGoogle Scholar
  3. 3.
    Ludwig JA, Weinstein JN. Biomarkers in cancer staging, prognosis and treatment selection. Nat Rev Cancer. 2005;5:845–56.CrossRefPubMedGoogle Scholar
  4. 4.
    Sawyers CL. The cancer biomarker problem. Nature. 2008;452:548–52.CrossRefPubMedGoogle Scholar
  5. 5.
    Wang K, Liu L, Zhu ZM, Shao JH, Xin L. Five polymorphisms of vascular endothelial growth factor (VEGF) and risk of breast cancer: a meta-analysis involving 16,703 individuals. Cytokine. 2011;56:167–73.CrossRefPubMedGoogle Scholar
  6. 6.
    Carpini JD, Karam AK, Montgomery L. Vascular endothelial growth factor and its relationship to the prognosis and treatment of breast, ovarian, and cervical cancer. Angiogenesis. 2010;13:43–58.CrossRefPubMedGoogle Scholar
  7. 7.
    Yoshiji H, Gomez D, Shibuya M, Thorgeirsson U. Expression of vascular endothelial growth factor, its receptor, and other angiogenic factors in human breast cancer. Cancer Res. 1996;56:2013–6.PubMedGoogle Scholar
  8. 8.
    Dabrosin C. Positive correlation between estradiol and vascular endothelial growth factor but not fibroblast growth factor-2 in normal human breast tissue in vivo. Clin Cancer Res. 2005;11:8036–41.CrossRefPubMedGoogle Scholar
  9. 9.
    Heikkila K, Ebrahim S, Lawlor DA. A systematic review of the association between circulating concentrations of C reactive protein and cancer. J Epidemiol Community Health. 2007;61:824–33.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Gauldie J, Richards C, Harnish D, Lansdorp P, Baumann H. Interferon beta 2/B-cell stimulatory factor type 2 shares identity with monocyte-derived hepatocyte-stimulating factor and regulates the major acute phase protein response in liver cells. Proc Natl Acad Sci. 1987;84:7251–5.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Allin KH, Nordestgaard BG, Flyger H, Bojesen SE. Elevated pre-treatment levels of plasma C-reactive protein are associated with poor prognosis after breast cancer: a cohort study. Breast Cancer Res. 2011;13:R55.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Das RL, Pathangey LB, Tinder TL, Schettini JL, Gruber HE, Mukherjee P. Breast-cancer-associated metastasis is significantly increased in a model of autoimmune arthritis. Breast Cancer Res. 2009;11:R56.CrossRefGoogle Scholar
  13. 13.
    Al Murri AM, Bartlett JM, Canney PA, Doughty JC, Wilson C, McMillan DC. Evaluation of an inflammation-based prognostic score (GPS) in patients with metastatic breast cancer. Br J Cancer. 2006;94:227–30.CrossRefPubMedGoogle Scholar
  14. 14.
    Pasanisi P, Venturelli E, Morelli D, Fontana L, Secreto G, Berrino F. Serum insulin-like growth factor-I and platelet-derived growth factor as biomarkers of breast cancer prognosis. Cancer Epidemiol Biomarkers Prev. 2008;17:1719–22.CrossRefPubMedGoogle Scholar
  15. 15.
    Lin Y, Huang R, Chen I, Li S, Shi Q, Jordan C, et al. Identification of interleukin-8 as estrogen receptor-regulated factor involved in breast cancer invasion and angiogenesis by protein arrays. Int J Cancer. 2004;109:507–15.CrossRefPubMedGoogle Scholar
  16. 16.
    Negus RP, Balkwill FR. Cytokines in tumour growth, migration and metastasis. World J Urol. 1996;14:157–65.CrossRefPubMedGoogle Scholar
  17. 17.
    Cohen T, Nahari D, Cerem LW, Neufeld G, Levi BZ. Interleukin 6 induces the expression of vascular endothelial growth factor. J Biol Chem. 1996;271:736–41.CrossRefPubMedGoogle Scholar
  18. 18.
    Lin MT, Lin BR, Chang CC, Chu CY, Su HJ, Chen ST, et al. IL-6 induces AGS gastric cancer cell invasion via activation of the c-Src/RhoA/ROCK signaling pathway. Int J Cancer. 2007;120:2600–8.CrossRefPubMedGoogle Scholar
  19. 19.
    FIGO. International Federation of Gynaecoloy and Obstetrics. Annual report and results of treatment in gynecologic cancer. Int J Gynaecol Obstet. 1989;28:189–90.CrossRefGoogle Scholar
  20. 20.
    Poncelet C, Fauvet R, Yazbeck C, Coutant C, Darai E. Impact of serum tumor marker determination on the management of women with borderline ovarian tumors: multivariate analysis of a French multicentre study. EJSO. 2010;36:1066–72.CrossRefPubMedGoogle Scholar
  21. 21.
    Engelstaedter V, Heublein S, Schumacher AL, Lenhard M, Engelstaedter H, Andergassen U, et al. Mucin-1 and its relation to grade, stage and survival in ovarian carcinoma patients. BMC Cancer. 2012;12:1–9.CrossRefGoogle Scholar
  22. 22.
    Verheul HM, Pinedo HM. The importance of platelet counts and their contents in cancer. Clin Cancer Res. 2003;7:32193221.Google Scholar
  23. 23.
    Wynendaele W, Derua R, Hoylaerts MF. Vascular endothelial growth factor measured in platelet poor plasma allows optimal separation between cancer patients and volunteers: a key to study an angiogenic marker in vivo? Ann Oncol. 1999;10:965–71.CrossRefPubMedGoogle Scholar
  24. 24.
    Lee JK, Hong YJ, Han CJ, Hwang DY, Hong SI. Clinical usefulness of serum and plasma vascular endothelial growth factor in cancer patients: which is the optimal specimen? Int J Oncol. 2000;17:149–52.PubMedGoogle Scholar
  25. 25.
    Adams J, Cander PJ, Downey S. Vascular endothelial growth factor (VEGF) in breast cancer: comparison of plasma, serum, and tissue VEGF and microvessel density and effects of tamoxifen. Cancer Res. 2000;60:2898–905.PubMedGoogle Scholar
  26. 26.
    Berezov TT, Ovchinnikova LK, Kuznetsova OM, Karabekova ZK, Vorotnikov IK, Tuleuova AA. Vascular endothelial growth factor in the serum of breast cancer patients. Bull Exp Biol Med. 2009;148:419–24.CrossRefPubMedGoogle Scholar
  27. 27.
    Jakubowska A, Gronwald J, Menklszak J, Gorski B, Huzarski T, Byrski T. The VEGF_936_C > T 3′ UTR polymorphism reduces BRCA1-associated breast cancer risk in Polish women. Cancer Lett. 2008;262:71–6.CrossRefPubMedGoogle Scholar
  28. 28.
    Ravishankaran P, Karunanithi R. Clinical significance of preoperative serum interleukin-6 and C-reactive protein level in breast cancer patients. World J Surg Oncol. 2011;9:18.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Al Murri AM, Wilson C, Lannigan A, Doughty JC, Angerson WJ, McArdle CS, et al. Evaluation of the relationship between the systemic inflammatory response and cancer-specific survival in patients with primary operable breast cancer. Br J Cancer. 2007;96:891–5.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell. 2010;140:883–99.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Leek RD, Lewis CE, Whitehouse R, Greenall M, Clarke J, Harris AL. Association of macrophage infiltration with angiogenesis and prognosis in invasive breast carcinoma. Cancer Res. 1996;56:4625–9.PubMedGoogle Scholar
  32. 32.
    Liao D, Luo Y, Markowitz D, Xiang R, Reisfeld RA. Cancer associated fibroblasts promote tumour growth and metastasis by modulating the tumour immune microenvironment in a 4T1 murine breast cancer model. PLoS One. 2009;4:e7965.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Ginestier C, Liu S, Diebel ME, Korkaya H, Luo M, Brown M, et al. CXCR1 blockade selectively targets human breast cancer stem cells in vitro and in xenografts. J Clin Invest. 2010;120:485–97.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Sawatsri S, Samid D, Malkapuram S, Sidell N. Inhibition of estrogen dependent breast cell responses with phenylacetate. Int J Cancer. 2001;93:687–92.CrossRefPubMedGoogle Scholar
  35. 35.
    Skoog L, Humla S, Axelsson M, Frost M, Norman A, Nordenskjold B, et al. Estrogen receptor levels and survival of breast cancer patients. A study on patients participating in randomized trials of adjuvant therapy. Acta Oncol. 1987;26:95–100.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Samia A. Ahmed
    • 1
  • Manal A. Hamed
    • 1
  • Omar S. Omar
    • 2
  1. 1.Therapeutic Chemistry DepartmentNational Research CentreCairoEgypt
  2. 2.Breast Cancer Clinic, Department of SurgeryCairo University HospitalCairoEgypt

Personalised recommendations