Skip to main content

Advertisement

SpringerLink
Log in

Prediction of breast cancer risk with volatile biomarkers in breath

  • Clinical trial
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Background

Human breath contains volatile organic compounds (VOCs) that are biomarkers of breast cancer. We investigated the positive and negative predictive values (PPV and NPV) of breath VOC biomarkers as indicators of breast cancer risk.

Methods

We employed ultra-clean breath collection balloons to collect breath samples from 54 women with biopsy-proven breast cancer and 124 cancer-free controls. Breath VOCs were analyzed with gas chromatography (GC) combined with either mass spectrometry (GC MS) or surface acoustic wave detection (GC SAW). Chromatograms were randomly assigned to a training set or a validation set. Monte Carlo analysis identified significant breath VOC biomarkers of breast cancer in the training set, and these biomarkers were incorporated into a multivariate algorithm to predict disease in the validation set. In the unsplit dataset, the predictive algorithms generated discriminant function (DF) values that varied with sensitivity, specificity, PPV and NPV.

Results

Using GC MS, test accuracy = 90% (area under curve of receiver operating characteristic in unsplit dataset) and cross-validated accuracy = 77%. Using GC SAW, test accuracy = 86% and cross-validated accuracy = 74%. With both assays, a low DF value was associated with a low risk of breast cancer (NPV > 99.9%). A high DF value was associated with a high risk of breast cancer and PPV rising to 100%.

Conclusion

Analysis of breath VOC samples collected with ultra-clean balloons detected biomarkers that accurately predicted risk 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
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Health, United States (2015) Centers for Disease Control and Prevention National Center for Health Statistics

  2. Jiang Y, Miglioretti DL, Metz CE, Schmidt RA (2007) Breast cancer detection rate: designing imaging trials to demonstrate improvements. Radiology 243:360–367

    Article  PubMed  Google Scholar 

  3. White A, Miller J, Royalty J et al (2015) Clinical outcomes of mammography in the National Breast and Cervical Cancer Early Detection Program, 2009–2012. Cancer Causes Control 26:723–732

    Article  PubMed  PubMed Central  Google Scholar 

  4. Cardoso MJ, Cardoso F (2017) Editorial: overdoing in breast cancer: the risks of over-screening, over-diagnosing and over-treating the disease. Breast 31:260

    Article  PubMed  Google Scholar 

  5. Pace LE, Keating NL (2014) A systematic assessment of benefits and risks to guide breast cancer screening decisions. JAMA 311:1327–1335

    Article  PubMed  CAS  Google Scholar 

  6. Mangler M, Freitag C, Lanowska M, Staeck O, Schneider A, Speiser D (2012) Volatile organic compounds (VOCs) in exhaled breath of patients with breast cancer in a clinical setting. Ginekol Pol 83:730–736

    PubMed  Google Scholar 

  7. Patterson SG, Bayer CW, Hendry RJ et al (2011) Breath analysis by mass spectrometry: a new tool for breast cancer detection? Am Surg 77:747–751

    PubMed  Google Scholar 

  8. Peng G, Hakim M, Broza YY et al (2010) Detection of lung, breast, colorectal, and prostate cancers from exhaled breath using a single array of nanosensors. Br J Cancer 103:542–551

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Xu Y, Lee H, Hu Y, Huang J, Kim S, Yun M (2013) Detection and identification of breast cancer volatile organic compounds biomarkers using highly-sensitive single nanowire array on a chip. J Biomed Nanotechnol 9:1164–1172

    Article  PubMed  CAS  Google Scholar 

  10. McCulloch M, Jezierski T, Broffman M, Hubbard A, Turner K, Janecki T (2006) Diagnostic accuracy of canine scent detection in early- and late-stage lung and breast cancers. Integr Cancer Ther 5:30–39

    Article  PubMed  Google Scholar 

  11. Phillips M, Cataneo R, Ditkoff B et al (2003) Volatile markers of breast cancer in the breath. Breast J 9:184–191

    Article  PubMed  Google Scholar 

  12. Phillips M, Cataneo RN, Ditkoff BA et al (2006) Prediction of breast cancer using volatile biomarkers in the breath. Breast Cancer Res Treat 99:19–21

    Article  PubMed  CAS  Google Scholar 

  13. Phillips M, Cataneo RN, Saunders C, Hope P, Schmitt P, Wai J (2010) Volatile biomarkers in the breath of women with breast cancer. J Breath Res 4:026003

    Article  PubMed  CAS  Google Scholar 

  14. Phillips M, Beatty JD, Cataneo RN et al (2014) Rapid point-of-care breath test for biomarkers of breast cancer and abnormal mammograms. PLoS ONE 9:e90226

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Phillips M, Cataneo R, Lebauer C, Mundada M, Saunders C (2016) Breath mass ion biomarkers of breast cancer. J Breath Res 11(1):016004

    Article  Google Scholar 

  16. Jezierska-Drutel A, Rosenzweig SA, Neumann CA (2013) Role of oxidative stress and the microenvironment in breast cancer development and progression. Adv Cancer Res 119:107–125

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Balliet RM, Capparelli C, Guido C et al (2011) Mitochondrial oxidative stress in cancer-associated fibroblasts drives lactate production, promoting breast cancer tumor growth: understanding the aging and cancer connection. Cell Cycle 10:4065–4073

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Kneepkens CM, Ferreira C, Lepage G, Roy CC (1992) The hydrocarbon breath test in the study of lipid peroxidation: principles and practice. Clin Invest Med 15:163–186

    PubMed  CAS  Google Scholar 

  19. Kneepkens CM, Lepage G, Roy CC (1994) The potential of the hydrocarbon breath test as a measure of lipid peroxidation. Free Radic Biol Med 17:127–160

    Article  PubMed  CAS  Google Scholar 

  20. Aghdassi E, Allard JP (2000) Breath alkanes as a marker of oxidative stress in different clinical conditions. Free Radic Biol Med 28:880–886

    Article  PubMed  CAS  Google Scholar 

  21. Spink DC, Katz BH, Hussain MM et al (2002) Induction of CYP1A1 and CYP1B1 in T-47D human breast cancer cells by benzo[a]pyrene is diminished by arsenite. Drug Metab Dispos 30:262–269

    Article  PubMed  CAS  Google Scholar 

  22. Brueggemeier RW, Diaz-Cruz ES (2006) Relationship between aromatase and cyclooxygenases in breast cancer: potential for new therapeutic approaches. Minerva Endocrinol 31:13–26

    PubMed  CAS  Google Scholar 

  23. Phillips M (2017) Inventor USPTO Application no. 20170188887. Ultra-clean bag or balloon for collection of volatile organic compounds in breath or air, USA. https://www.google.com/patents/US20170188887

  24. Phillips M (1997) Method for the collection and assay of volatile organic compounds in breath. Anal Biochem 247:272–278

    Article  PubMed  CAS  Google Scholar 

  25. Phillips M, Altorki N, Austin JH et al (2008) Detection of lung cancer using weighted digital analysis of breath biomarkers. Clin Chim Acta 393:76–84

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Hanley JA, McNeil BJ (1982) The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology 143:29–36

    Article  PubMed  CAS  Google Scholar 

  27. A Prospective Validation Study of a Rapid Point-of-Care Breath Test for Breast Cancer (2017) National Institutes of Health https://clinicaltrials.gov/ct2/show/NCT02888366

  28. Li J, Peng Y, Liu Y et al (2014) Investigation of potential breath biomarkers for the early diagnosis of breast cancer using gas chromatography-mass spectrometry. Clin Chim Acta 436:59–67

    Article  PubMed  CAS  Google Scholar 

  29. Miekisch W, Herbig J, Schubert JK (2012) Data interpretation in breath biomarker research: pitfalls and directions. J Breath Res 6:036007

    Article  PubMed  CAS  Google Scholar 

  30. Silva CL, Perestrelo R, Silva P, Tomas H, Camara JS (2017) Volatile metabolomic signature of human breast cancer cell lines. Sci Rep 7:43969

    Article  PubMed  PubMed Central  Google Scholar 

  31. Centers for Disease Control & Prevention: Cancer among women. http://www.cdc.gov/cancer/dcpc/data/women.htm

  32. National Cancer Institute: Breast cancer. http://www.cancer.gov/cancertopics/types/breast

Download references

Acknowledgements

Michael Phillips is President and CEO of Menssana Research, Inc. Schmitt & Associates, Newark, NJ, maintained a database of chromatograms and Daniel Strano analyzed the data. We thank Jan Huston MD (deceased) for her sustained support and encouragement, and for coordinating the clinical study at Hackensack UMC Mountainside. Omar Ornelas of Grupo Mexlab performed GC SAW analysis of eight samples from Universidad de Guadalajara & Instituto Jalisciense de Cancerologia. Menssana Research Inc has no commercial, scientific, or other relationships with Ornelas or Grupo Mexlab or their affiliates.

Author information

Author notes

  1. Deceased: Jan Huston.

Authors and Affiliations

  1. Breath Research Laboratory, Menssana Research Inc, 211 Warren St, Newark, NJ, 07103, USA

    Michael Phillips, Renee N. Cataneo & Sonali Pathak

  2. Department of Medicine, New York Medical College, Valhalla, NY, USA

    Michael Phillips

  3. Universidad de Guadalajara & Instituto Jalisciense de Cancerologia, 44280, Guadalajara, Mexico

    Jose Alfonso Cruz-Ramos

  4. Formerly Hackensack UMC Mountainside, Montclair, NJ, USA

    Jan Huston

  5. Grupo Mexlab, Paseos Del Sol, 45070, Zapopan, Jalisco, Mexico

    Omar Ornelas

  6. Saint Michael’s Medical Center, Newark, NJ, USA

    Nadine Pappas

Authors
  1. Michael Phillips
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Renee N. Cataneo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jose Alfonso Cruz-Ramos
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jan Huston
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Omar Ornelas
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nadine Pappas
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sonali Pathak
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michael Phillips.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Phillips, M., Cataneo, R.N., Cruz-Ramos, J.A. et al. Prediction of breast cancer risk with volatile biomarkers in breath. Breast Cancer Res Treat 170, 343–350 (2018). https://doi.org/10.1007/s10549-018-4764-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-018-4764-4

Keywords

Search

Navigation