Detection of cancer through exhaled breath: a systematic review

Agne Krilaviciute, Jonathan Alexander Heiss, Marcis Leja, Juozas Kupcinskas, Hossam Haick and Hermann Brenner _

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Oncotarget. 2015; 6:38643-38657. https://doi.org/10.18632/oncotarget.5938

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Agne Krilaviciute1, Jonathan Alexander Heiss1, Marcis Leja2, Juozas Kupcinskas3, Hossam Haick4 and Hermann Brenner1,5,6

1 Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany

2 Faculty of Medicine, University of Latvia, Digestive Diseases Center GASTRO, and Riga East University Hospital, Riga, Latvia

3 Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania

4 Department of Chemical Engineering and Russell Berrie Nanotechnology Institute, Technion – Israel Institute of Technology, Haifa, Israel

5 Division of Preventive Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

6 German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany

Correspondence to:

Hossam Haick, email:

Keywords: breath analysis, cancer detection, volatile organic compound, VOC, systematic review

Received: August 03, 2015 Accepted: September 01, 2015 Published: September 30, 2015


Background: Timely diagnosis of cancer represents a challenging task; in particular, there is a need for reliable non-invasive screening tools that could achieve high levels of adherence at virtually no risk in population-based screening. In this review, we summarize the current evidence of exhaled breath analysis for cancer detection using standard analysis techniques and electronic nose.

Methods: Relevant studies were identified searching Pubmed and Web of Science databases until April 30, 2015. Information on breath test performance, such as sensitivity and specificity, was extracted together with volatile compounds that were used to discriminate cancer patients from controls. Performance of different breath analysis techniques is provided for various cancers together with information on methodological issues, such as breath sampling protocol and validation of the results.

Results: Overall, 73 studies were included, where two-thirds of the studies were conducted on lung cancer. Good discrimination usually required a combination of multiple biomarkers, and area under the receiver operating characteristic curve or accuracy reached levels of 0.9 or higher in multiple studies. In 25% of the reported studies, classification models were built and validated on the same datasets. Huge variability was seen in different aspects among the studies.

Conclusions: Analyses of exhaled breath yielded promising results, although standardization of breath collection, sample storage and data handling remain critical issues. In order to foster breath analysis implementation into practice, larger studies should be implemented in true screening settings, paying particular attention to standardization in breath collection, consideration of covariates, and validation in independent population samples.

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