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. © 2014 Phillips et al.