Skip to main content

Advertisement

Log in

Analysis of blood markers for early breast cancer diagnosis

  • Research Article
  • Published:
Clinical and Translational Oncology Aims and scope Submit manuscript

Abstract

Purpose

Breast cancer is the most common neoplasm in women and has the highest associated mortality rate. Rapid detection programmes can provide early diagnosis and increase the chances of survival. There are no specific tumor biomarkers for the early phase of the disease. The primary aim of this study was to search a blood biomarker with levels that exceeded the normal range established in the general population that could be used to screen breast cancer.

Methods/patients

Case–control study. Conventional as well as research (NGAL, EGFR and 8-OHdG) tumor biomarkers were analyzed.

Results

A total of 126 women were enrolled (cases: 63 patients with local breast cancer; Controls: 63 healthy women). Significant differences were found in patients with higher levels of the conventional markers, Ca15.3, CEA, Cyfra 21.1 and NSE. However, when commercial cut-off values were used, only Ca 15.13 was significant. In the group of research biomarkers, significantly higher levels of EGFR were found in the control group, and of 8-OHdG in the case group. Using logistic regression analysis and a ROC curve, an equation composed of five markers, Ca 15.3, NSE, NGAL, EGFR and 8-OHdG, which yielded a correct diagnostic probability of breast cancer of 91.8% was obtained.

Conclusions

8-OHdG has been identified as a new potential marker for screening early stage breast cancer. In addition, a model that combines five blood markers that can be used as a diagnostic test in certain groups of patients has been developed. New studies with a larger sample size are needed to verify the results obtained.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC Cancer Base No. 11, Lyon, France: International Agency for Research on Cancer. 2013. http://globocan.iarc.fr, Accessed 5 May 2017.

  2. Siu AL. Screening for breast cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2016;164:279–96.

    Article  PubMed  Google Scholar 

  3. Melnikow J, Fenton JJ, Whitlock EP, Miglioretti DL, Weyrich MS, Thompson JH, et al. Supplemental screening for breast cancer in women with dense breasts: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med. 2016;164:268–78.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Miller AB, Wall C, Baines CJ, Sun P, To T, Narod SA. Twenty-five-year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial. BMJ. 2014;348:g366.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Harris L, Fritsche H, Mennel R, Norton L, Ravdin P, Taube S, et al. American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol. 2007;25:5287–312.

    Article  CAS  PubMed  Google Scholar 

  6. Khatcheressian JL, Hurley P, Bantug E, Esserman LJ, Grunfeld E, Halberg F, et al. Breast cancer follow-up and management after primary treatment: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2013;31:961–5.

    Article  CAS  PubMed  Google Scholar 

  7. Sturgeon CM, Duffy MJ, Stenman UH, Lilja H, Brünner N, Chan DW, et al. National academy of clinical biochemistry laboratory medicine practice guidelines for use of tumor markers in testicular, prostate, colorectal, breast, and ovarian cancers. Clin Chem. 2008;54:e11–79.

    Article  CAS  PubMed  Google Scholar 

  8. Ramsey SD, Henry NL, Gralow JR, Mirick DK, Barlow W, Etzioni R, et al. Tumor marker usage and medical care costs among older early stage breast cancer survivors. J Clin Oncol. 2014;33:149–55.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Thriveni K, Krishnamoorthy L, Ramaswamy G. Correlation study of carcino embryonic antigen & cancer antigen 15.3 in pretreated female breast cancer patients. Indian J Clin Biochem. 2007;22:57–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Shao Y, Sun X, He Y, Liu C, Liu H. Elevated levels of serum tumor markers CEA and CA15-3 are prognostic parameters for different molecular subtypes of breast cancer. PLoS One. 2015;10:e0133830. doi:10.1371/journal.pone.0133830.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Molina R, Auge JM, Farrus B, Zanón G, Pahisa J, Muñoz M, et al. Prospective evaluation of carcinoembryonic antigen (CEA) and carbohydrate antigen 15.3 (CA 15.3) in patients with primary locoregional breast cancer. Clin Chem. 2010;56:1148–57.

    Article  CAS  PubMed  Google Scholar 

  12. Moazzezy N, Farahany TZ, Oloomi M, Bouzari S. Relationship between preoperative serum CA15-3 and CEA levels and clinicopathological parameters in breast cancer. Asian Pac J Cancer Prev. 2014;15:1685–8.

    Article  PubMed  Google Scholar 

  13. Li H, Chen K, Su F, Song E, Gong C. Preoperative CA 15-3 levels predict the prognosis of nonmetastatic luminal A breast cancer. J Surg Res. 2014;189:48–56.

    Article  CAS  PubMed  Google Scholar 

  14. Ali HQ, Mahdi NK, Al-Jowher MH. The value of CA15-3 in diagnosis, prognosis and treatment response in women with breast cancer. J Pak Med Assoc. 2013;63:1138–41.

    PubMed  Google Scholar 

  15. Wu SG, He ZY, Zhou J, Sun JY, Li FY, Lin Q, et al. Serum levels of CEA and CA15-3 in different molecular subtypes and prognostic value in Chinese breast cancer. Breast. 2014;23:88–93.

    Article  PubMed  Google Scholar 

  16. Mårtensson J, Bell M, Xu S, Bottai M, Ravn B, Venge P, et al. Association of plasma neutrophil gelatinase-associated lipocalin (NGAL) with sepsis and acute kidney dysfunction. Biomarkers. 2013;18:349–56.

    Article  PubMed  Google Scholar 

  17. Wenners AS, Mehta K, Loibl S, Park H, Mueller B, Arnold N, et al. Neutrophil gelatinase associated lipocalin (NGAL) predicts response to neoadjuvant chemotherapy and clinical outcome in primary human breast cancer. PLoS One. 2012;7:e45826.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Tas F, Bilgin E, Karabulut S, Duranyildiz D. Clinical significance of serum epidermal growth factor receptor (EGFR) levels in patients with breast cancer. Cytokine. 2015;71:66–70.

    Article  CAS  PubMed  Google Scholar 

  19. Pande D, Negi R, Karki K, Khanna S, Khanna RS, Khanna HD. Oxidative damage markers as possible discriminatory biomarkers in breast carcinoma. Transl Res. 2012;160:411–8.

    Article  CAS  PubMed  Google Scholar 

  20. Valavanidis A, Vlachogianni T, Fiotakis C. 8-hydroxy-2-deoxyguanosine(8-OHdG): a critical biomarker of oxidative stress and carcinogenesis. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2009;27:120–39.

    Article  CAS  PubMed  Google Scholar 

  21. Grupo Español de Investigación en Cáncer de Mama. Proyecto El Álamo III. Encuesta de evolución de pacientes con cáncer de mama en hospitales del grupo GEICAM; 1998–2001. 2014. http://www.guiasalud.es/GPC/GPC_538_AF%20GUIA%20GEICAM_resumida.pdf. Accessed 15 Jan 2017.

  22. Lumachi F, Basso SM, Brandes AA, Pagano D, Ermani M. Relationship between tumor markers CEA and CA 15–3, TNM staging, estrogen receptor rate and MIB-1 index in patients with pT1-2 breast cancer. Anticancer Res. 2004;24:3221–4.

    CAS  PubMed  Google Scholar 

  23. Asgeirsson KS, Agrawal A, Allen C, Hitch A, Ellis IO, Chapman C, et al. Serum epidermal growth factor receptor and HER2 expression in primary and metastatic breast cancer patients. Breast Cancer Res. 2007;9:R75.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Li CI. Discovery and validation of breast cancer early detection biomarkers in preclinical samples. Horm Cancer. 2011;2:125–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Nelson HD, Pappas M, Cantor A, Griffin J, Daeges M, Humphrey L. Harms of breast cancer screening: systematic review to update the 2009 U.S. preventive services task force recommendation. Ann Intern Med. 2016;164(4):256–67.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to J. Bayo.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Research involving human participants and/or animals

The study was approved by the Ethics Committee of the Biomedical Research in Huelva (Spain). As previously indicated, all patients consent in writing to participate in the study. Annex (informed consent) includes both the information sheet and the informed consent completed by the participants. Researchers in the study kept confidentiality of the data of all the patients included in the study and ensured compliance with the law Organic Law 15/1999 on the Protection of Personal Data and any future regulation that legislates the confidentiality of the data. The information regarding the identity of the patients was considered to be confidential for all purposes. Data from the patients collected on the data collection sheet have been registered anonymously. Likewise, the database generated in the study, has been managed by the principal investigator of study and does contained personal identification data. During the course of this research, all documents related to the questionnaires have been located in a safe and locked area of the hospital.

Appendix: Informed consent

Appendix: Informed consent

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bayo, J., Castaño, M.A., Rivera, F. et al. Analysis of blood markers for early breast cancer diagnosis. Clin Transl Oncol 20, 467–475 (2018). https://doi.org/10.1007/s12094-017-1731-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12094-017-1731-1

Keywords

Navigation