Abstract
BackgroundPrevious 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.Methods244 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.ResultsPerformance 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).ConclusionsA 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.
Highlights
Breast cancer is the most commonly diagnosed cancer in women, in whom it is second only to lung cancer as a cause of cancer death [1]
The objective of this study was to test the hypothesis that a rapid point-of-care breath test could detect breath biomarkers of breast cancer
Subjects were excluded if they had a previous history of breast cancer, cancer at any other site, breast biopsy, abnormal mammogram or palpable breast mass
Summary
Breast cancer is the most commonly diagnosed cancer in women, in whom it is second only to lung cancer as a cause of cancer death [1]. In order to reduce the number of breast cancer deaths, many countries have established screening mammography programs to detect and treat early-stage disease [3]. Screening mammography may be associated with an increased risk of radiation-induced breast cancer, as well as with overdiagnosis and overtreatment [4,5]. 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.
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