Skip to main content

Advertisement

SpringerLink
Log in

Salivary biomarkers in breast cancer: a cross-sectional study

  • Original Article
  • Published:
Supportive Care in Cancer Aims and scope Submit manuscript

A Correction to this article was published on 18 November 2020

This article has been updated

Abstract

Aim

The objective was to evaluate the diagnostic value of salivary biomarkers in breast cancer.

Materials and methods

A prospective study was carried out of 91 consecutive breast cancer patients and 60 controls without neoplastic disease. Demographic data were recorded, along with the Hospital Anxiety Depression (HAD), risk for development periodontal diseases questionnaire and Mini-Nutritional Assessment (MNA) scores, and the TNM classification and stage of the primary tumor. Unstimulated basal saliva samples were collected and stored at − 80 °C until analysis.

Results

The mean salivary CA125 concentration was 102.1 pg/ml in the control group and 267.6 pg/ml in the breast cancer group (p = 0.005). The soluble Fas (sFas) concentration in turn was 84.1 pg/ml and 145.9 pg/ml, respectively (p = 0.008). None of the biomarkers was related to questionnaire-assessed risk for development of periodontal diseases. The area under the ROC curve was 0.68 for CA125 (95% CI, 0.05–0.56) and 0.67 for sFas (95% CI, 0.08–0.55).

Conclusions

The salivary biomarkers CA125 and sFas appear to be promising tools in the diagnosis of breast cancer.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Change history

  • 18 November 2020

    Incorrect authornames.

References

  1. DeSantis CE, Bray F, Ferlay J et al (2015) International variation in female breast cancer incidence and mortality rates. Cancer Epidemiol Biomark Prev 24:1495–1506. https://doi.org/10.1158/1055-9965.EPI-15-0535

    Article  Google Scholar 

  2. Howell A, Anderson AS, Clarke RB, Duffy SW, Evans DG, Garcia-Closas M, Gescher AJ, Key TJ, Saxton JM, Harvie MN (2014) Risk determination and prevention of breast cancer. Breast Cancer Res 16:446. https://doi.org/10.1186/s13058-014-0446-2

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. McPherson K, Steel CM, Dixon JM (2000) ABC of breast diseases. Breast cancer-epidemiology, risk factors, and genetics. BMJ 321:624–628. https://doi.org/10.1136/bmj.321.7261.624

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Sledge GW, Mamounas EP, Hortobagyi GN, Burstein HJ, Goodwin PJ, Wolff AC (2014) Past, present, and future challenges in breast cancer treatment. J Clin Oncol 32:1979–1986. https://doi.org/10.1200/JCO.2014.55.4139

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Kaczor-Urbanowicz KE, Martín Carreras-Presas C, Kaczor T, Tu M, Wei F, Garcia-Godoy F, Wong DTW (2017) Emerging technologies for salivaomics in cancer detection. J Cell Mol Med 21:640–647. https://doi.org/10.1111/jcmm.13007

    Article  PubMed  CAS  Google Scholar 

  6. Marić P, Ozretić P, Levanat S, Oresković S, Antunac K, Beketić-Oresković L (2011) Tumor markers in breast cancer--evaluation of their clinical usefulness. Coll Antropol 35:241–247

    PubMed  Google Scholar 

  7. Porika M, Malotu N, Veldandi UK, Yadala N, Abbagani S (2010) Evaluation of tumor markers in southern Indian breast cancer patients. Asian Pac J Cancer Prev 11:157–159

    PubMed  Google Scholar 

  8. Liu X, Yu H, Qiao Y, Yang J, Shu J, Zhang J, Zhang Z, He J, Li Z (2018) Salivary glycopatterns as potential biomarkers for screening of early-stage breast cancer. EBioMedicine 28:70–79. https://doi.org/10.1016/J.EBIOM.2018.01.026

    Article  PubMed  PubMed Central  Google Scholar 

  9. Streckfus C, Bigler L (2005) The use of soluble, salivary c- erb B-2 for the detection and post-operative follow-up of breast cancer in women: the results of a five-year translational research study. Adv Dent Res 18:17–24. https://doi.org/10.1177/154407370501800105

    Article  PubMed  CAS  Google Scholar 

  10. Streckfus C, Bigler L (2002) Saliva as a diagnostic fluid. Oral Dis 8:69–76. https://doi.org/10.1034/j.1601-0825.2002.1o834.x

    Article  PubMed  CAS  Google Scholar 

  11. Porto-Mascarenhas EC, Assad DX, Chardin H, Gozal D, de Luca Canto G, Acevedo AC, Guerra ENS (2017) Salivary biomarkers in the diagnosis of breast cancer: a review. Crit Rev Oncol Hematol 110:62–73. https://doi.org/10.1016/J.CRITREVONC.2016.12.009

    Article  PubMed  Google Scholar 

  12. Sugimoto M, Wong DT, Hirayama A, Soga T, Tomita M (2010) Capillary electrophoresis mass spectrometry-based saliva metabolomics identified oral, breast and pancreatic cancer-specific profiles. Metabolomics 6:78–95. https://doi.org/10.1007/s11306-009-0178-y

    Article  PubMed  CAS  Google Scholar 

  13. Pfaffe T, Cooper-White J, Beyerlein P, Kostner K, Punyadeera C (2011) Diagnostic potential of saliva: current state and future applications. Clin Chem 57:675–687. https://doi.org/10.1373/clinchem.2010.153767

    Article  PubMed  CAS  Google Scholar 

  14. Liu J, Duan Y (2012) Saliva: a potential media for disease diagnostics and monitoring. Oral Oncol 48:569–577. https://doi.org/10.1016/J.ORALONCOLOGY.2012.01.021

    Article  PubMed  Google Scholar 

  15. Serrano J, Herrera D (2011) Evaluación de un cuestionario para la asignación del riesgo individual en el desarrollo de las enfermedades periodontales. Periodoncia Osteointegración 21:133–142

    Google Scholar 

  16. Guigoz Y, Vellas B, Garry PJ (2009) Assessing the nutritional status of the elderly: the mini nutritional assessment as part of the geriatric evaluation. Nutr Rev 54:S59–S65. https://doi.org/10.1111/j.1753-4887.1996.tb03793.x

    Article  Google Scholar 

  17. Zigmond AS, Snaith RP (1983) The hospital anxiety and depression scale. Acta Psychiatr Scand 67:361–370. https://doi.org/10.1111/j.1600-0447.1983.tb09716.x

    Article  PubMed  CAS  Google Scholar 

  18. Navazesh M, Kumar SKS, University of Southern California School of Dentistry (2008) Measuring salivary flow: challenges and opportunities. J Am Dent Assoc 139(Suppl):35S–40S. https://doi.org/10.14219/jada.archive.2008.0353

    Article  PubMed  Google Scholar 

  19. Contreras-Aguilar MD, Escribano D, Martínez-Subiela S, Martínez-Miró S, Rubio M, Tvarijonaviciute A, Tecles F, Cerón JJ (2017) Influence of the way of reporting alpha-amylase values in saliva in different naturalistic situations: a pilot study. PLoS One 12:e0180100. https://doi.org/10.1371/journal.pone.0180100

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Tvarijonaviciute A, Aznar-Cayuela C, Rubio CP, Ceron JJ, López-Jornet P (2017) Evaluation of salivary oxidate stress biomarkers, nitric oxide and C-reactive protein in patients with oral lichen planus and burning mouth syndrome. J Oral Pathol Med 46:387–392. https://doi.org/10.1111/jop.12522

    Article  PubMed  CAS  Google Scholar 

  21. Jocelyn PC (1987) Spectrophotometric assay of thiols. In: Methods in enzymology. pp 44–67

  22. Tecles F, Tvarijonaviciute A, De Torre C et al (2016) Total esterase activity in human saliva: validation of an automated assay, characterization and behaviour after physical stress. Scand J Clin Lab Invest 76:324. https://doi.org/10.3109/00365513.2016.1163417

    Article  PubMed  CAS  Google Scholar 

  23. Muraoka T, Katsuramaki T, Shiraishi H, Yokoyama MM (1990) Automated enzymatic measurement of adenosine deaminase isoenzyme activities in serum. Anal Biochem 187:268–272. https://doi.org/10.1016/0003-2697(90)90455-i

    Article  PubMed  CAS  Google Scholar 

  24. Barranco T, Rubio CP, Tvarijonaviciute A et al (2019) Changes of salivary biomarkers under different storage conditions: effects of temperature and length of storage. Biochem Medica 29:94–111. https://doi.org/10.11613/BM.2019.010706

    Article  Google Scholar 

  25. Brooks MN, Wang J, Li Y, Zhang R, Elashoff D, Wong D (2008) Salivary protein factors are elevated in breast cancer patients. Mol Med Rep 1:375–378. https://doi.org/10.3892/mmr.1.3.375

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Glazer CA, Chang SS, Ha PK, Califano JA (2009) Applying the molecular biology and epigenetics of head and neck cancer in everyday clinical practice. Oral Oncol 45:440–446. https://doi.org/10.1016/J.ORALONCOLOGY.2008.05.013

    Article  PubMed  CAS  Google Scholar 

  27. Bast RC, Badgwell D, Lu Z et al (2005) New tumor markers: CA125 and beyond. Int J Gynecol Cancer 15:274–281. https://doi.org/10.1111/j.1525-1438.2005.00441.x

    Article  PubMed  Google Scholar 

  28. Balan JJ, Rao RS, Premalatha BR, Patil S (2012) Analysis of tumor marker CA 125 in saliva of normal and oral squamous cell carcinoma patients: a comparative study. J Contemp Dent Pract 13:671–675. https://doi.org/10.5005/jp-journals-10024-1207

    Article  PubMed  Google Scholar 

  29. Tay SK, Chua EK (1994) Correlation of serum, urinary and salivary CA 125 levels in patients with adnexal masses. Ann Acad Med Singap 23:311–314

    PubMed  CAS  Google Scholar 

  30. Chen DX, Schwartz PE, Li FQ (1990) Saliva and serum CA 125 assays for detecting malignant ovarian tumors. Obstet Gynecol 75:701–704

    PubMed  CAS  Google Scholar 

  31. Zhang K-Y, Liu C-Y, Hua L, Wang SL, Li J (2016) Clinical evaluation of salivary carbohydrate antigen 125 and leptin in controls and parotid tumours. Oral Dis 22:630–638. https://doi.org/10.1111/odi.12505

    Article  PubMed  Google Scholar 

  32. Nagler R, Bahar G, Shpitzer T, Feinmesser R (2006) Concomitant analysis of salivary tumor markers--a new diagnostic tool for oral cancer. Clin Cancer Res 12:3979–3984. https://doi.org/10.1158/1078-0432.CCR-05-2412

    Article  PubMed  CAS  Google Scholar 

  33. Laffont A, Goussot V, Berriolo-Riedinger A, Riedinger J-M (2018) CA 125 assay in the extension assessment of newly diagnosed breast cancers: why and how? Ann Biol Clin (Paris) 76:553–561. https://doi.org/10.1684/abc.2018.1368

    Article  Google Scholar 

  34. Papoff G, Cascino I, Eramo A et al (1996) An N-terminal domain shared by Fas/Apo-1 (CD95) soluble variants prevents cell death in vitro. J Immunol 156:4622–4630

    PubMed  CAS  Google Scholar 

  35. Cheng J, Zhou T, Liu C et al (1994) Protection from Fas-mediated apoptosis by a soluble form of the Fas molecule. Science 263(80):1759–1762. https://doi.org/10.1126/science.7510905

    Article  PubMed  CAS  Google Scholar 

  36. Ueno T, Toi M, Tominaga T (1999) Circulating soluble Fas concentration in breast cancer patients. Clin Cancer Res 5:3529–3533

    PubMed  CAS  Google Scholar 

  37. Sheen-Chen S-M, Chen H-S, Eng H-L, Chen W-J (2003) Circulating soluble Fas in patients with breast cancer. World J Surg 27:10–13. https://doi.org/10.1007/s00268-002-6378-5

    Article  PubMed  Google Scholar 

  38. Papapanou PN, Sanz M, Buduneli N, Dietrich T, Feres M, Fine DH, Flemmig TF, Garcia R, Giannobile WV, Graziani F, Greenwell H, Herrera D, Kao RT, Kebschull M, Kinane DF, Kirkwood KL, Kocher T, Kornman KS, Kumar PS, Loos BG, Machtei E, Meng H, Mombelli A, Needleman I, Offenbacher S, Seymour GJ, Teles R, Tonetti MS (2018) Periodontitis: consensus report of workgroup 2 of the 2017 world workshop on the classification of periodontal and peri-implant diseases and conditions. J Periodontol 89:S173–S182. https://doi.org/10.1002/JPER.17-0721

    Article  PubMed  Google Scholar 

  39. Berglundh T, Armitage G, Araujo MG, Avila-Ortiz G, Blanco J, Camargo PM, Chen S, Cochran D, Derks J, Figuero E, Hämmerle CHF, Heitz-Mayfield LJA, Huynh-Ba G, Iacono V, Koo KT, Lambert F, McCauley L, Quirynen M, Renvert S, Salvi GE, Schwarz F, Tarnow D, Tomasi C, Wang HL, Zitzmann N (2018) Peri-implant diseases and conditions: consensus report of workgroup 4 of the 2017 world workshop on the classification of periodontal and peri-implant diseases and conditions. J Periodontol 89:S313–S318. https://doi.org/10.1002/JPER.17-0739

    Article  PubMed  Google Scholar 

  40. Jepsen S, Caton JG, Albandar JM, Bissada NF, Bouchard P, Cortellini P, Demirel K, de Sanctis M, Ercoli C, Fan J, Geurs NC, Hughes FJ, Jin L, Kantarci A, Lalla E, Madianos PN, Matthews D, McGuire MK, Mills MP, Preshaw PM, Reynolds MA, Sculean A, Susin C, West NX, Yamazaki K (2018) Periodontal manifestations of systemic diseases and developmental and acquired conditions: consensus report of workgroup 3 of the 2017 world workshop on the classification of periodontal and peri-implant diseases and conditions. J Clin Periodontol 45:S219–S229. https://doi.org/10.1111/jcpe.12951

    Article  PubMed  Google Scholar 

  41. Hoon Tan P, Ellis I, Allison K, Brogi E, Fox SB, Lakhani S, Lazar AJ, Morris EA, Sahin A, Salgado R, Sapino A, Sasano H, Schnitt S, Sotiriou C, van Diest P, White VA, Lokuhetty D, Cree IA, The WHO Classification of Tumours Editorial Board (2020) The 2019 WHO classification of tumours of the breast. Histopathology. https://doi.org/10.1111/his.14091

  42. Arias-Bujanda N, Regueira-Iglesias A, Balsa-Castro C, Nibali L, Donos N, Tomás I (2019) Accuracy of single molecular biomarkers in saliva for the diagnosis of periodontitis: a systematic review and meta-analysis. J Clin Periodontol 47:2–18. https://doi.org/10.1111/jcpe.13202

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Faculty of Medicine and Odontology, Hospital Morales Meseguer, Clínica Odontológica, Marqués del los Vélez s/n, 30008, Murcia, Spain

    Pía López-Jornet & Cristina Aznar

  2. Hospital Morales Meseguer, Clínica Odontológica Universitaria, Medicina Oral, 2 planta ADV, Marques de los velez s/n, 30008, Murcia, Spain

    Pía López-Jornet

  3. Interdisciplinary Laboratory of Clinical Analysis Interlab-UMU, Regional Campus of International Excellence Campus Mare Nostrum, University of Murcia, Murcia, Spain

    Jose Ceron & Tvarijonaviciute Asta

Authors
  1. Pía López-Jornet
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cristina Aznar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jose Ceron
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tvarijonaviciute Asta
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pía López-Jornet.

Ethics declarations

The study was approved by the local Clinical Research Ethics Committee (Reference no. 2003/2018).

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

López-Jornet, P., Aznar, C., Ceron, J. et al. Salivary biomarkers in breast cancer: a cross-sectional study. Support Care Cancer 29, 889–896 (2021). https://doi.org/10.1007/s00520-020-05561-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00520-020-05561-3

Keywords

Search

Navigation