|Year : 2017 | Volume
| Issue : 2 | Page : 33-36
Assessment of some biomarkers of inflammation in breast cancer patients in Benin City, Nigeria
Eboreime Ofunre1, Atoe Kenneth2, Idemudia Joseph Osagie2
1 Department of Surgery, Central Hospital, University of Benin Teaching Hospital, Benin City, Nigeria
2 Department of Chemical Pathology, University of Benin Teaching Hospital, Benin City, Nigeria
|Date of Web Publication||23-May-2019|
Dr. Idemudia Joseph Osagie
Department of Chemical Pathology, University of Benin Teaching Hospital, Benin City
Source of Support: None, Conflict of Interest: None
Introduction: Inflammation has been shown to play a major role in the pathogenesis of most malignancies including breast cancer. The inflammatory basis of breast cancer has not been evaluated in our environment. Objective: The purpose of this study is to determine the level of some biomarkers of systemic inflammation in patients with breast cancer compared to those of apparently healthy subjects without the disease in Benin City, Nigeria. Methodology: This is a case control study conducted in Benin City, Edo State, Nigeria. Breast cancer patients from Central hospital, Benin City and controls from the general population had their venous blood sampled and analyzed for Erythrocyte Sedimentation Rate (ESR) and C-Reactive Proteins (CRP) levels using standardized laboratory methods. Data were analyzed using SPSS (version 17). Results: Results showed a statistical significant increase (P < 0.05) in both ESR and CRP levels of patients with breast cancer compared to the control. There is also a significant positive correlation (P < 0.001) between ESR and CRP in the study population. Conclusion: These findings support the fact that inflammation is a risk factor for the development of breast cancer and this association might be of clinical significance as these inflammation markers might be of prognostic value.
Keywords: Breast cancer, C-reactive protein, erythrocyte sedimentation rate, inflammation Breast cancer, C-reactive protein, erythrocyte sedimentation rate, inflammation
|How to cite this article:|
Ofunre E, Kenneth A, Osagie IJ. Assessment of some biomarkers of inflammation in breast cancer patients in Benin City, Nigeria. Niger J Surg Sci 2017;27:33-6
|How to cite this URL:|
Ofunre E, Kenneth A, Osagie IJ. Assessment of some biomarkers of inflammation in breast cancer patients in Benin City, Nigeria. Niger J Surg Sci [serial online] 2017 [cited 2019 Oct 15];27:33-6. Available from: http://www.njssjournal.org/text.asp?2017/27/2/33/258801
| Introduction|| |
Breast cancer is the most common type of cancer in women and the leading cause of cancer-related death worldwide. The exact cause of breast cancer is not completely known; it represents a complex interplay of genetic susceptibility and environmental factor, and inflammation has been shown to increase the risk of cancer.,, The inflammatory response promotes carcinogenesis by damaging DNA, stimulating angiogenesis and cell proliferation, and inhibiting apoptosis.,
Erythrocyte sedimentation rate (ESR) is a simple inexpensive index of measurement of chronic inflammation frequently ordered in clinical medicine.,, In cancer management, a high ESR has been found to correlate with the prognosis of breast cancer and other types of cancer such as Hodgkin's disease, gastric carcinoma, renal cell carcinoma, chronic lymphocytic leukemia, colorectal cancer, and prostate cancer.,, The diagnostic use of ESR has been generally replaced by the measurement of C-reactive protein (CRP).
CRP is a classical positive acute-phase protein displaying rapid and pronounced rise of its plasma concentration in response to acute inflammation, infection, and tissue damage., CRP is produced by the liver, predominantly under transcriptional control by the cytokine interleukin-6 originating from the site of pathology.
Serum CRP has been shown to parallel carcinogenesis possibly as an expression of the host defense reaction or as paraneoplastic syndrome., Previous epidemiologic studies have reported that elevated CRP levels may be associated with a poor prognosis of several types of solid cancers, including endometrial, cervical, colorectal, pancreatic, hepatocellular, esophageal, renal cell, bladder, prostate, ovarian, and non-small cell lung cancer., Breast cancers are characterized by significant histological inflammation; emerging evidence suggests that inflammatory pathways also play an important role in breast cancer progression.,,,,, Hence, the aim of the present study was to measure the levels of inflammatory markers in breast cancer patients by measuring their ESR and CRP levels compared to those without the disease (control).
| Patients and Methods|| |
A total of sixty female participants from Central Hospital, Benin City, were recruited for this study between July 1, 2011 and October, 31, 2012, a period of 15 months. Thirty of these women (50%) had breast cancer and were of both pre- and post-menopausal age groups. The other thirty participants (50%) were age-matched apparently healthy women who served as control. The study was approved by the Ethics Committee of Central Hospital, Benin City, and participation was voluntary.
Biochemical assay was done at the Department of Chemical Pathology, University of Benin Teaching Hospital.
Sample collection and preparation
Venous blood was obtained from participants into an anticoagulant bottle containing ethylenediaminetetraacetic acid (EDTA) for ESR evaluation, and also into a sterile plain bottle, which was allowed to clot and retract, and then the serum was harvested after centrifugation at 3000 rpm for 15 min for CRP evaluation. The venous blood samples were collected after the patients were diagnosed with breast cancer before the commencement of chemotherapy.
ESR level was evaluated in the whole blood in the EDTA bottle immediately, while the harvested sera were stored frozen at –20°C until CRP analysis was carried out.
Determination of erythrocyte sedimentation rate
ESR was determined using the Westergren method,, which measures the distance that erythrocytes have sediment after 1 h in a vertical column of anticoagulated blood under the influence of gravity.
Determination of C-reactive protein levels
CRP levels were determined using the immunoturbidimetric method. In this method, CRP sample binds to specific anti-CRP antibodies, which have been adsorbed to latex particles, and the agglutination measured spectrophotometrically is proportional to the quantity of CRP in the sample.
Data analysis was conducted using the general linear model of SAS 2004 model version 9.1.3 Inc. Cary, North Carolina, USA. All results were expressed as mean ± standard error of mean. Multiple group comparison was performed by one-way ANOVA followed by Duncan test. Pearson's correlation coefficient was employed to ascertain the association between various inflammatory markers.
| Results|| |
The mean age of the participants with breast cancer was 55 ± 1.6 years (range: 45–65), while that of the controls was 51 ± 1.4 years (range: 42–66) as shown in [Table 1]. ESR of the participants with breast cancer was 47.50 ± 7.269 mm/h (range: 14–130) and this was statistically significant (P < 0.05) when compared to that of the controls which was 6.867 ± 0.525 mm/h (range: 3–13). CRP level of participants with breast cancer was 73.763 ± 1.331 mg/dL (59.860–82.760) and that of the controls was 8.955 ± 0.657 mg/dL (5.460–13.920) and this disparity was statistically significant (P < 0.05).
|Table 1: The mean age, erythrocyte sedimentation rate, and C-reactive proteins levels of breast cancer patients and those without the disease (control)|
Click here to view
There is also a significant positive correlation (P < 0.001) between ESR and CRP levels (r = 0.6004) in all the participants as shown in [Table 2]. [Figure 1] showed remarkable differences in the levels of the inflammatory biomarkers(ESR and CRP) in patients with breast cancer and those without breast cancer (control subjects).
|Table 2: Correlation coefficients of C-reactive proteins and erythrocyte sedimentation rate in breast cancer patients and controls|
Click here to view
|Figure 1: Histogram comparing levels of erythrocyte sedimentation rate and C-reactive protein of breast cancer patients with normal controls|
Click here to view
| Discussion|| |
The findings in this study showed statistically significant elevation of ESR levels of patients with breast cancer compared to that of the controls. High ESR levels have been found to correlate with overall poor prognosis for different types of cancer including breast. European studies of patients with Hodgkin's disease have suggested that an elevated ESR may still be an excellent predictor of early relapse, especially if the value remained elevated after chemotherapy or failed to drop to a normal level within 6 months after therapy.,
Findings from this study also showed statistically significantly elevated CRP levels in breast cancer patients compared to the controls; this is probably due to the rise in the plasma concentration of interleukin-6 which is produced predominantly by macrophages during inflammation. High serum CRP might reflect a high metastatic potential as inflammatory cytokines in general and CRP in particular are known to promote metastatic spread by stimulating angiogenesis, increasing vascular permeability, and acting as an endothelial cell mitogen. Results from prospective epidemiologic studies are conflicting, with some other studies showing an association between elevated CRP levels and poor prognosis, and others showing no such association., The largest study so far comprised 700 women treated successfully for early-stage breast cancer and found to have elevated levels of CRP measured 2½ years from the time of diagnosis with reduced disease and overall survival.
Studies carried out by Allin and Nordestgaard suggest that invasive breast cancer patients with elevated CRP levels at diagnosis had a 1–7-fold increased risk of death from breast cancer compared to patients with low CRP levels at diagnosis. Promising data on the prognostic significance of serum CRP in various malignancies have been reported. Studies carried out by Akanni et al. at Osogbo, Nigeria, reported a rise in CRP levels in patients with chronic myeloid leukemia; they concluded that CRP could be a useful factor in determining disease progression or monitoring the effectiveness of treatment in leukemic patients.
Studies conducted by Jo et al. in Abeokuta, South Western Nigeria, reported that patients with high CRP also had significantly elevated ESR, a finding which is in keeping with our studies.
| Conclusion|| |
Our study confirms the importance of ESR and CRP in breast cancer management. ESR and CRP levels are not routinely measured when planning breast cancer treatment, and the need for baseline determination of these inflammatory markers cannot be underestimated as they might help surgeons know about the patients' prognosis and so guide treatment decision.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Coughlin SS, Ekwueme DU. Breast cancer as a global health concern. Cancer Epidemiol 2009;33:315-8.
McKeown N. Antioxidants and breast cancer. Nutr Rev 1999;57:321-4.
Helzlsouer KJ, Erlinger TP, Platz EA. C-reactive protein levels and subsequent cancer outcomes: Results from a prospective cohort study. Eur J Cancer 2006;42:704-7.
Balkwill F, Mantovani A. Inflammation and cancer: Back to Virchow? Lancet 2001;357:539-45.
Fleming JS, Beaugié CR, Haviv I, Chenevix-Trench G, Tan OL. Incessant ovulation, inflammation and epithelial ovarian carcinogenesis: Revisiting old hypotheses. Mol Cell Endocrinol 2006;247:4-21.
Jackson JR, Seed MP, Kircher CH, Willoughby DA, Winkler JD. The codependence of angiogenesis and chronic inflammation. FASEB J 1997;11:457-65.
Saadeh C. The erythrocyte sedimentation rate: Old and new clinical applications. South Med J 1998;91:220-5.
Brigden M. The erythrocyte sedimentation rate. Still a helpful test when used judiciously. Postgrad Med 1998;103:257-62, 272-4.
Sox HC Jr., Liang MH. The erythrocyte sedimentation rate. Guidelines for rational use. Ann Intern Med 1986;104:515-23.
Ljungberg B, Grankvist K, Rasmuson T. Serum acute phase reactants and prognosis in renal cell carcinoma. Cancer 1995;76:1435-9.
Johansson JE, Sigurdsson T, Holmberg L, Bergström R. Erythrocyte sedimentation rate as a tumor marker in human prostatic cancer. An analysis of prognostic factors in 300 population-based consecutive cases. Cancer 1992;70:1556-63.
Henry-Amar M, Friedman S, Hayat M, Somers R, Meerwaldt JH, Carde P, et al.
Erythrocyte sedimentation rate predicts early relapse and survival in early-stage Hodgkin disease. The EORTC Lymphoma Cooperative Group. Ann Intern Med 1991;114:361-5.
Johnson AM. Amino acids, peptide and proteins. In: Burtis CA, Ashwood ER, Bruns DE, editors. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 4th
ed., Vol. 23. St. Louis, MO: Elsevier Saunders; 2006. p. 555-6.
Pepys MB, Hirschfield GM. C-reactive protein: A critical update. J Clin Invest 2003;111:1805-12.
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 U S A 1987;84:7251-5.
Marnell L, Mold C, Du Clos TW. C-reactive protein: Ligands, receptors and role in inflammation. Clin Immunol 2005;117:104-11.
Deodhar SD. C-reactive protein: The best laboratory indicator available for monitoring disease activity. Cleve Clin J Med 1989;56:126-30.
Allin KH, Bojesen SE, Nordestgaard BG. Baseline C-reactive protein is associated with incident cancer and survival in patients with cancer. J Clin Oncol 2009;27:2217-24.
Schmid M, Schneitter A, Hinterberger S, Seeber J, Reinthaller A, Hefler L. Association of elevated C-reactive protein levels with an impaired prognosis in patients with surgically treated endometrial cancer. Obstet Gynecol 2007;110:1231-6.
Polterauer S, Grimm C, Tempfer C, Sliutz G, Speiser P, Reinthaller A, et al.
C-reactive protein is a prognostic parameter in patients with cervical cancer. Gynecol Oncol 2007;107:114-7.
O'Dowd C, McRae LA, McMillan DC, Kirk A, Milroy R. Elevated preoperative C-reactive protein predicts poor cancer specific survival in patients undergoing resection for non-small cell lung cancer. J Thorac Oncol 2010;5:988-92.
Roxburgh CS, McMillan DC. Role of systemic inflammatory response in predicting survival in patients with primary operable cancer. Future Oncol 2010;6:149-63.
Das Roy L, 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.
DeNardo DG, Coussens LM. Inflammation and breast cancer. Balancing immune response: Crosstalk between adaptive and innate immune cells during breast cancer progression. Breast Cancer Res 2007;9:212.
Ginestier C, Liu S, Diebel ME, Korkaya H, Luo M, Brown M, et al.
CXCR1 blockade selectively targets human breast cancer stem cellsin vitro
and in xenografts. J Clin Invest 2010;120:485-97.
Leek RD, Lewis CE, Whitehouse R, Greenall M, Clarke J, Harris AL, et al.
Association of macrophage infiltration with angiogenesis and prognosis in invasive breast carcinoma. Cancer Res 1996;56:4625-9.
Liao D, Luo Y, Markowitz D, Xiang R, Reisfeld RA. Cancer associated fibroblasts promote tumor growth and metastasis by modulating the tumor immune microenvironment in a 4T1 murine breast cancer model. PLoS One 2009;4:e7965.
Mantovani A, Marchesi F, Porta C, Sica A, Allavena P. Inflammation and cancer: Breast cancer as a prototype. Breast 2007;16 Suppl 2:S27-33.
Böttiger LE, Svedberg CA. Normal erythrocyte sedimentation rate and age. Br Med J 1967;2:85-7.
Rifal N, Tracy RP, Ridker PM. Clinical efficiency of an automated high sensitive C- reactive protein Assay. Clin Chem 2003;45;363-9.
Eberhard OK, Langefeld I, Kuse ER, Brunkhorst FM, Kliem V, Schlitt HJ, et al.
Procalcitonin in the early phase after renal transplantation – Will it add to diagnostic accuracy? Clin Transplant 1998;12:206-11.
Al Murri AM, Bartlett JM, Canney PA, Doughty JC, Wilson C, McMillan DC, et al.
Evaluation of an inflammation-based prognostic score (GPS) in patients with metastatic breast cancer. Br J Cancer 2006;94:227-30.
Abuquerque KV, Price MR, Badley RA, Jonup I, Pearson D, Blamey RW, et al
. Pretreatment serum level of tumour makers in metastatic breast cancer; a prospective assessment of their role in predicting response to therapy and survival. Eur J Surg Oncol 1995,24;504-9.
Pierce BL, Ballard-Barbash R, Bernstein L, Baumgartner RN, Neuhouser ML, Wener MH, et al.
Elevated biomarkers of inflammation are associated with reduced survival among breast cancer patients. J Clin Oncol 2009;27:3437-44.
Williams MR, Turkes A, Pearson D, Griffiths K, Blamey RW. An objective biochemical assessment of therapeutic response in metastatic breast cancer: A study with external review of clinical data. Br J Cancer 1990;61:126-32.
Allin KH, Nordestgaard BG. Elevated C-reactive protein in the diagnosis, prognosis, and cause of cancer. Crit Rev Clin Lab Sci 2011;48:155-70.
Kodama J, Miyagi Y, Seki N, Tokumo K, Yoshinouchi M, Kobashi Y, et al.
Serum C-reactive protein as a prognostic factor in patients with epithelial ovarian cancer. Eur J Obstet Gynecol Reprod Biol 1999;82:107-10.
Akanni EO, Mabayoje VO, Oseni BS, Ajani OO. C-reactive protein and tumour marker (Ferritin) levels in chronic myeloid leukaemia patients. Am Eur J Sci Res 2010;5:31-8.
Jo DA, Talabi OA. C-reactive protein in hospital patients in South-Western Nigeria community. J Natl Sci Eng Tech 2010;9:106-14.
[Table 1], [Table 2]