Breast Cancer Research and Treatment

, Volume 170, Issue 2, pp 343–350 | Cite as

Prediction of breast cancer risk with volatile biomarkers in breath

  • Michael Phillips
  • Renee N. Cataneo
  • Jose Alfonso Cruz-Ramos
  • Jan Huston
  • Omar Ornelas
  • Nadine Pappas
  • Sonali Pathak
Clinical trial



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.


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.


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%.


Analysis of breath VOC samples collected with ultra-clean balloons detected biomarkers that accurately predicted risk of breast cancer.


Breath Breast cancer Volatile organic compound Biomarker 



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.


  1. 1.
    Health, United States (2015) Centers for Disease Control and Prevention National Center for Health StatisticsGoogle Scholar
  2. 2.
    Jiang Y, Miglioretti DL, Metz CE, Schmidt RA (2007) Breast cancer detection rate: designing imaging trials to demonstrate improvements. Radiology 243:360–367CrossRefPubMedGoogle Scholar
  3. 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 26:723–732CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Cardoso MJ, Cardoso F (2017) Editorial: overdoing in breast cancer: the risks of over-screening, over-diagnosing and over-treating the disease. Breast 31:260CrossRefPubMedGoogle Scholar
  5. 5.
    Pace LE, Keating NL (2014) A systematic assessment of benefits and risks to guide breast cancer screening decisions. JAMA 311:1327–1335CrossRefPubMedGoogle Scholar
  6. 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 83:730–736PubMedGoogle Scholar
  7. 7.
    Patterson SG, Bayer CW, Hendry RJ et al (2011) Breath analysis by mass spectrometry: a new tool for breast cancer detection? Am Surg 77:747–751PubMedGoogle Scholar
  8. 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 103:542–551CrossRefPubMedPubMedCentralGoogle Scholar
  9. 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 9:1164–1172CrossRefPubMedGoogle Scholar
  10. 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 5:30–39CrossRefPubMedGoogle Scholar
  11. 11.
    Phillips M, Cataneo R, Ditkoff B et al (2003) Volatile markers of breast cancer in the breath. Breast J 9:184–191CrossRefPubMedGoogle Scholar
  12. 12.
    Phillips M, Cataneo RN, Ditkoff BA et al (2006) Prediction of breast cancer using volatile biomarkers in the breath. Breast Cancer Res Treat 99:19–21CrossRefPubMedGoogle Scholar
  13. 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 4:026003CrossRefPubMedGoogle Scholar
  14. 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:e90226CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Phillips M, Cataneo R, Lebauer C, Mundada M, Saunders C (2016) Breath mass ion biomarkers of breast cancer. J Breath Res 11(1):016004CrossRefGoogle Scholar
  16. 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 119:107–125CrossRefPubMedPubMedCentralGoogle Scholar
  17. 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 10:4065–4073CrossRefPubMedPubMedCentralGoogle Scholar
  18. 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 15:163–186PubMedGoogle Scholar
  19. 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 17:127–160CrossRefPubMedGoogle Scholar
  20. 20.
    Aghdassi E, Allard JP (2000) Breath alkanes as a marker of oxidative stress in different clinical conditions. Free Radic Biol Med 28:880–886CrossRefPubMedGoogle Scholar
  21. 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 30:262–269CrossRefPubMedGoogle Scholar
  22. 22.
    Brueggemeier RW, Diaz-Cruz ES (2006) Relationship between aromatase and cyclooxygenases in breast cancer: potential for new therapeutic approaches. Minerva Endocrinol 31:13–26PubMedGoogle Scholar
  23. 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.
  24. 24.
    Phillips M (1997) Method for the collection and assay of volatile organic compounds in breath. Anal Biochem 247:272–278CrossRefPubMedGoogle Scholar
  25. 25.
    Phillips M, Altorki N, Austin JH et al (2008) Detection of lung cancer using weighted digital analysis of breath biomarkers. Clin Chim Acta 393:76–84CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Hanley JA, McNeil BJ (1982) The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology 143:29–36CrossRefPubMedGoogle Scholar
  27. 27.
    A Prospective Validation Study of a Rapid Point-of-Care Breath Test for Breast Cancer (2017) National Institutes of Health
  28. 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 436:59–67CrossRefPubMedGoogle Scholar
  29. 29.
    Miekisch W, Herbig J, Schubert JK (2012) Data interpretation in breath biomarker research: pitfalls and directions. J Breath Res 6:036007CrossRefPubMedGoogle Scholar
  30. 30.
    Silva CL, Perestrelo R, Silva P, Tomas H, Camara JS (2017) Volatile metabolomic signature of human breast cancer cell lines. Sci Rep 7:43969CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Centers for Disease Control & Prevention: Cancer among women.
  32. 32.
    National Cancer Institute: Breast cancer.

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Breath Research LaboratoryMenssana Research IncNewarkUSA
  2. 2.Department of MedicineNew York Medical CollegeValhallaUSA
  3. 3.Universidad de Guadalajara & Instituto Jalisciense de CancerologiaGuadalajaraMexico
  4. 4.Formerly Hackensack UMC MountainsideMontclairUSA
  5. 5.Grupo MexlabZapopanMexico
  6. 6.Saint Michael’s Medical CenterNewarkUSA

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