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CEA in breast ductal secretions as a promising biomarker for the diagnosis of breast cancer: a systematic review and meta-analysis

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Abstract

Purpose

Other studies have shown that levels of carcinoembryonic antigen (CEA) in breast ductal secretions (BDS) differ significantly between breast cancer (BC) patients and healthy individuals, providing direct evidence for CEA in BDS as a promising biomarker for BC. This meta-analysis was designed to assess the potential diagnostic value of CEA in BDS.

Methods

Relevant articles were retrieved from Embase, Pubmed, and the Cochrane Library. Sensitivity, specificity, and diagnostic odds ratio (DOR) of CEA in BDS for diagnosing BC were pooled using random effects models. SROC and the area under the curve (AUC) were used to estimate overall diagnostic performance.

Results

This meta-analysis comprised five studies with a total of 340 BC patients and 448 healthy controls. For CEA in BDS, the pooled sensitivity, specificity, and DOR to diagnose BC were 58 % [95 % confidence interval (CI): 52–63 %], 87 % (95 % CI: 84–90 %), and 7.07 (95 % CI: 3.10–16.12), respectively. Moreover, the AUC of CEA in the diagnosis of BC was 0.8570.

Conclusions

CEA in BDS is a promising biomarker in the diagnosis of BC and should be evaluated as a standard screening tool upon verification of our results in a larger study population.

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References

  1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893–917.

    Article  CAS  PubMed  Google Scholar 

  2. Fan L, Strasser-Weippl K, Li JJ, St Louis J, Finkelstein DM, Yu KD, et al. Breast cancer in China. Lancet Oncol. 2014;15:e279–89.

    Article  PubMed  Google Scholar 

  3. Gewefel H, Salhia B. Breast cancer in adolescent and young adult women. Clin Breast Cancer. 2014;14:390–5.

    Article  PubMed  Google Scholar 

  4. World Health Organization. WHO position paper on mammography screening. Geneva, Switzerland, 1st ed. 2014.

  5. Mannello F. Analysis of the intraductal microenvironment for the early diagnosis of breast cancer: identification of biomarkers in nipple-aspirate fluids. Expert Opin Med Diagn. 2008;2:1221–31.

    Article  CAS  PubMed  Google Scholar 

  6. Mannello F, Medda V, Tonti GA. Protein profile analysis of the breast microenvironment to differentiate healthy women from breast cancer patients. Expert Rev Proteom. 2009;6:43–60.

    Article  CAS  Google Scholar 

  7. Mannello F, Tonti GA, Canestrari F. Nutrients and nipple aspirate fluid composition: the breast microenvironment regulates protein expression and cancer aetiology. Genes Nutr. 2008;3:77–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Sauter ER, Ross E, Daly M, Klein-Szanto A, Engstrom PF, Sorling A, et al. Nipple aspirate fluid: a promising non-invasive method to identify cellular markers of breast cancer risk. Br J Cancer. 1997;76:494–501.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Gold P, Freedman SO. Specific carcinoembryonic antigens of the human digestive system. J Exp Med. 1965;122:467–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Kahana L, Bartal AH, Yechieli H, Guttman I, Sheinfeld M. Carcinoembryonic-like substance in breast fluid discharge in benign and malignant breast disease and in milk of lactating women. Isr J Med Sci. 1981;17:1035–40.

    CAS  PubMed  Google Scholar 

  11. Inaji H, Yayoi E, Maeura Y, Matsuura N, Tominaga S, Koyama H, et al. Carcinoembryonic antigen estimation in nipple discharge as an adjunctive tool in the diagnosis of early breast cancer. Cancer. 1987;60:3008–13.

    Article  CAS  PubMed  Google Scholar 

  12. Mori T, Inaji H, Higashiyama M, Yayoi E, Izuo M, Ueno E, et al. Evaluation of dot-immunobinding assay for carcinoembryonic antigen determination in nipple discharge as an adjunct in the diagnosis of early breast cancer. Research Group for Carcinoembryonic Antigen in Nipple Discharge. Jpn J Clin Oncol. 1989;19:373–9.

    CAS  PubMed  Google Scholar 

  13. Inaji H, Koyama H, Motomura K, Noguchi S, Mori Y, Kimura Y, et al. ErbB-2 protein levels in nipple discharge: role in diagnosis of early breast cancer. Tumour Biol. 1993;14:271–8.

    Article  CAS  PubMed  Google Scholar 

  14. Foretova L, Garber JE, Sadowsky NL, Verselis SJ, Joseph DM, Andrade AF, et al. Carcinoembryonic antigen in breast nipple aspirate fluid. Cancer Epidemiol Biomark Prev. 1998;7:195–8.

    CAS  Google Scholar 

  15. Imayama S, Mori M, Ueo H, Nanbara S, Adachi Y, Mimori K, et al. Presence of elevated carcinoembryonic antigen on absorbent disks applied to nipple area of breast carcinoma patients. Cancer. 1996;78:1229–34.

    Article  CAS  PubMed  Google Scholar 

  16. Zhao Y, Verselis SJ, Klar N, Sadowsky NL, Kaelin CM, Smith B, et al. Nipple fluid carcinoembryonic antigen and prostate-specific antigen in cancer-bearing and tumor-free breasts. J Clin Oncol. 2001;19:1462–7.

    CAS  PubMed  Google Scholar 

  17. Lee A, Kim Y, Han K, Kang CS, Jeon HM, Shim SI. Detection of tumor markers including carcinoembryonic antigen, APC, and cyclin D2 in fine-needle aspiration fluid of breast. Arch Pathol Lab Med. 2004;128:1251–6.

    CAS  Google Scholar 

  18. Whiting PF, Rutjes AW, Westwood ME, Mallett S, Deeks JJ, Reitsma JB, et al. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med. 2011;155:529–36.

    Article  PubMed  Google Scholar 

  19. Zamora J, Abraira V, Muriel A, Khan K, Coomarasamy A. Meta-DiSc: a software for meta-analysis of test accuracy data. BMC Med Res Methodol. 2006;6:31.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Oda M, Makita M, Iwaya K, Akiyama F, Kohno N, Tsuchiya B, et al. High levels of DJ-1 protein in nipple fluid of patients with breast cancer. Cancer Sci. 2012;103:1172–6.

    Article  CAS  PubMed  Google Scholar 

  21. Wang G, Qin Y, Zhang J, Zhao J, Liang Y, Zhang Z, et al. Nipple discharge of CA15-3, CA125, CEA and TSGF as a new biomarker panel for breast cancer. Int J Mol Sci. 2014;15:9546–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Zhao YS, Pang D, Wang F, Xue YW, Gao DN, Li H, et al. Nipple aspirate fluid collection, related factors and relationship between carcinoembryonic antigen in nipple aspirate fluid and breast diseases in women in Harbin, PRC. Cancer Epidemiol Biomark Prev. 2009;18:732–8.

    Article  CAS  Google Scholar 

  23. Glas AS, Lijmer JG, Prins MH, Bonsel GJ, Bossuyt PM. The diagnostic odds ratio: a single indicator of test performance. J Clin Epidemiol. 2003;56:1129–35.

    Article  PubMed  Google Scholar 

  24. Jones CM, Athanasiou T. Summary receiver operating characteristic curve analysis techniques in the evaluation of diagnostic tests. Ann Thorac Surg. 2005;79:16–20.

    Article  PubMed  Google Scholar 

  25. Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50:1088–101.

    Article  CAS  PubMed  Google Scholar 

  26. Bleyer A, Welch HG. Effect of three decades of screening mammography on breast-cancer incidence. N Engl J Med. 2012;367:1998–2005.

    Article  CAS  PubMed  Google Scholar 

  27. Kaufmann M, von Minckwitz G, Bergh J, Conte PF, Darby S, Eiermann W, et al. Breakthroughs in research and treatment of early breast cancer: an overview of the last three decades. Arch Gynecol Obstet. 2013;288:1203–12.

    Article  PubMed  Google Scholar 

  28. Engel JM, Stankowski-Drengler TJ, Stankowski RV, Liang H, Doi SA, Onitilo AA. All-cause mortality is decreased in women undergoing annual mammography before breast cancer diagnosis. Am J Roentgenol. 2015;204:898–902.

    Article  Google Scholar 

  29. Irvin VL, Kaplan RM. Screening mammography & breast cancer mortality: meta-analysis of quasi-experimental studies. PLoS One. 2014;9:e98105.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Ali RM, England A, McEntee MF, Hogg P. A method for calculating effective lifetime risk of radiation-induced cancer from screening mammography. Int J Diagn Imagin Radiat Ther. 2015;21:298–303.

    Google Scholar 

  31. Loberg M, Lousdal ML, Bretthauer M, Kalager M. Benefits and harms of mammography screening. Breast Cancer Res. 2015;17:63.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Morrow M, Waters J, Morris E. MRI for breast cancer screening, diagnosis, and treatment. Lancet. 2011;378:1804–11.

    Article  PubMed  Google Scholar 

  33. Ahern CH, Shih YC, Dong W, Parmigiani G, Shen Y. Cost-effectiveness of alternative strategies for integrating MRI into breast cancer screening for women at high risk. Br J Cancer. 2014;111:1542–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Kuhajda FP, Offutt LE, Mendelsohn G. The distribution of carcinoembryonic antigen in breast carcinoma diagnostic and prognostic implications. Cancer. 1983;52:1257–64.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors thank Professor Gang-Ping Wang from Rizhao People’s Hospital (Shandong, China) for contributing individual patient data, and Xin Yang for providing invaluable advice throughout the data analyzing process. We are also grateful to the anonymous reviewers for their insightful comments and suggestions that helped improve the quality of our paper.

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Authors and Affiliations

  1. Department of Laboratory Medicine, The Third Affiliated Hospital of Guangxi University of Chinese Medicine, No. 32, Jie-Fang-Bei Rd, Cheng-Zhong District, Liuzhou, Guangxi, China

    Shifu Tang, Yifan Sun, Lili Wei, Shengbo Zhu, Renqi Yang & Yiyong Huang

  2. Department of Rheumatology, The Fourth Affiliated Hospital of Guangxi Medical University, Guangxi, China

    Fang Zhou

  3. Department of General Surgery, The Third Affiliated Hospital of Guangxi University of Chinese Medicine, Guangxi, China

    Jianqing Yang

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  1. Shifu Tang
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  2. Fang Zhou
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Correspondence to Shifu Tang.

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Tang, S., Zhou, F., Sun, Y. et al. CEA in breast ductal secretions as a promising biomarker for the diagnosis of breast cancer: a systematic review and meta-analysis. Breast Cancer 23, 813–819 (2016). https://doi.org/10.1007/s12282-016-0680-9

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  • DOI: https://doi.org/10.1007/s12282-016-0680-9

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