Rapid point-of-care breath test predicts breast cancer and abnormal mammograms in symptomatic women.

Abstract

Previous studies have reported volatile organic compounds (VOCs) in the breath as biomarkers of breast cancer. These biomarkers may be derived from cancer-associated fibroblasts, in which oxidative stress degrades polyunsaturated fatty acids to volatile alkanes and methylated alkane derivatives that are excreted in the breath. We evaluated a rapid point-of-care test for breath VOC biomarkers as predictors of breast cancer and abnormal mammograms. Methods: We studied 593 women aged ≥ 18 yr referred to three sites for mammography for a symptomatic breast-related concern (e.g. breast mass, nipple discharge). A rapid point-of-care breath testing system collected and concentrated alveolar breath VOCs on a sorbent trap and analyzed them with gas chromatography and surface acoustic wave detection in < 6 min. Breath VOC chromatograms were randomly assigned to a training set or to a validation set. Monte Carlo analysis identified significant breath VOC biomarkers of breast cancer and abnormal mammograms in the training set, and these biomarkers were incorporated into a multivariate algorithm to predict disease in the validation set. Results: Prediction of breast cancer: 50 women had biopsy-proven breast cancer (invasive cancer 41, ductal non-invasive cancer 9) Unsplit data set: Breath VOCs identified breast cancer with 83% accuracy (area under curve of receiver operating characteristic), 82% sensitivity and 77.1% specificity. Split data sets: Training set breath VOCs identified breast cancer with 80.3% accuracy, 84% sensitivity and 74.3% specificity. Corresponding values in the validation set were 68%% accuracy, 72.4% sensitivity and 61.5% specificity. Prediction of BIRADS 4 and 5 mammograms (versus BIRADS 1, 2 and 3): Unsplit data set: Breath VOCs identified abnormal mammograms with 76.2% accuracy. Split data sets: Breath VOCs identified abnormal mammograms with 74.2% accuracy, 73.3% sensitivity and 60% specificity. Corresponding values in the validation set were 60.5% accuracy, 64.2% sensitivity and 51% specificity. Conclusions: A rapid point-of-care test for breath VOC biomarkers predicted risk of breast cancer and abnormal mammograms in women with breast-related symptoms. .