title: Rapid point-of-care breath test for biomarkers of breast cancer and abnormal mammograms.
abstract: BACKGROUND
  Previous studies have reported volatile organic compounds (VOCs) in breath as biomarkers of breast cancer and abnormal mammograms, apparently resulting from increased oxidative stress and cytochrome p450 induction. We evaluated a six-minute point-of-care breath test for VOC biomarkers in women screened for breast cancer at centers in the USA and the Netherlands.
  
  
  METHODS
  244 women had a screening mammogram (93/37 normal/abnormal) or a breast biopsy (cancer/no cancer 35/79). A mobile point-of-care system collected and concentrated breath and air VOCs for analysis with gas chromatography and surface acoustic wave detection. Chromatograms were segmented into a time series of alveolar gradients (breath minus room air). Segmental alveolar gradients were ranked as candidate biomarkers by C-statistic value (area under curve [AUC] of receiver operating characteristic [ROC] curve). Multivariate predictive algorithms were constructed employing significant biomarkers identified with multiple Monte Carlo simulations and cross validated with a leave-one-out (LOO) procedure.
  
  
  RESULTS
  Performance of breath biomarker algorithms was determined in three groups: breast cancer on biopsy versus normal screening mammograms (81.8% sensitivity, 70.0% specificity, accuracy 79% (73% on LOO) [C-statistic value], negative predictive value 99.9%); normal versus abnormal screening mammograms (86.5% sensitivity, 66.7% specificity, accuracy 83%, 62% on LOO); and cancer versus no cancer on breast biopsy (75.8% sensitivity, 74.0% specificity, accuracy 78%, 67% on LOO).
  
  
  CONCLUSIONS
  A pilot study of a six-minute point-of-care breath test for volatile biomarkers accurately identified women with breast cancer and with abnormal mammograms. Breath testing could potentially reduce the number of needless mammograms without loss of diagnostic sensitivity.
authors.affiliation: Breath Research Laboratory, Menssana Research Inc., Newark, New Jersey, United States of America; Department of Medicine, New York Medical College, Valhalla, New York, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Phillips
authors.affiliation: Swedish Cancer Institute, Seattle, Washington, United States of America.
authors.forename: J David
authors.initials: JD
authors.lastname: Beatty
authors.affiliation: Breath Research Laboratory, Menssana Research Inc., Newark, New Jersey, United States of America.
authors.forename: Renee N
authors.initials: RN
authors.lastname: Cataneo
authors.affiliation: HackensackUMC Mountainside, Montclair, New Jersey, United States of America.
authors.forename: Jan
authors.initials: J
authors.lastname: Huston
authors.affiliation: Breath Research Laboratory, Menssana Research Inc., Newark, New Jersey, United States of America.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Kaplan
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, GROW School of Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Roy I
authors.initials: RI
authors.lastname: Lalisang
authors.affiliation: Department of Radiotherapy (MAASTRO), GROW School of Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Philippe
authors.initials: P
authors.lastname: Lambin
authors.affiliation: Department of Radiology, GROW School of Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Marc B I
authors.initials: MB
authors.lastname: Lobbes
authors.affiliation: Breath Research Laboratory, Menssana Research Inc., Newark, New Jersey, United States of America.
authors.forename: Mayur
authors.initials: M
authors.lastname: Mundada
authors.affiliation: Saint Michael's Medical Center, Newark, New Jersey, United States of America.
authors.forename: Nadine
authors.initials: N
authors.lastname: Pappas
authors.affiliation: Breath Research Laboratory, Menssana Research Inc., Newark, New Jersey, United States of America.
authors.forename: Urvish
authors.initials: U
authors.lastname: Patel
mesh_terms: D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism*; D001944:Breath Tests; D018270:Carcinoma, Ductal, Breast / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D006801:Humans; D008327:Mammography; D009010:Monte Carlo Method; D015999:Multivariate Analysis; D019095:Point-of-Care Systems; D012372:ROC Curve; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor