Exhaled Breath Tests for Cancer: 'Breath-omics' is a New Frontier in Biomarker Research

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Breath tests for cancer detection
Breath tests for cancer detection

The altered cellular metabolism of tumors and other diseased tissues yields altered chemical “fingerprints” of volatile waste products in the air exhaled by patients. These chemical “breath-prints” have the potential to open the door to handheld “electronic nose” technologies that will, developers hope, yield noninvasive real-time screening and diagnostic clinical tests for lung cancer, as well as cancers of the head and neck, breast, stomach, and other organs.

The “breath-omics” field is in its early days and it is not yet clear that metabolic signatures can reliably differentiate cancer types across large patient populations; yet early preclinical studies suggest that tumor histology, and possibly even tumor genotype, may indeed be discerned simply by chemically analyzing a patient's cough or sigh.  

One day, noninvasive breath tests could reduce the rate of unnecessary endoscopy and biopsy among patients suspected to harbor gastric cancer, suggests research published on March 5th in the British Journal of Cancer.1 The pilot study of 130 patients with gastric complaints found that analysis of volatile organic compound (VOC) patterns in patient breath samples allows differentiation between gastric cancers, peptic ulcers, and other benign stomach ailments—and even between early stage (1 and 2) and late stage (3 and 4) gastric cancers.1  Five VOCs were elevated in the breath samples of patients with gastric cancer and peptic ulcers:  2-propenenitrile, 2-butoxy-ethanol, furfural, 6-methyl-5-hepten-2-one, and isoprene.1  Potential confounding factors like alcohol or tobacco use, or gastric Helicobacter pylori infection, did not diminish the value of VOC breath-prints in identifying cases of gastric cancer, the authors noted.1 

“The preliminary results of this pilot study could open a new and promising avenue to diagnose gastric cancer and distinguish it from other gastric diseases,” they concluded.1

A multicenter clinical trial is now under way to confirm the utility of breath-prints in identifying patients who have gastric cancer.1

Additionally, two pilot studies in 2012 discovered that breath-prints can differentiate patients with lung cancer from healthy controls, also found that patients harboring small cell lung cancers could be differentiated from those with non-small cell lung cancer (NSCLC), and patients with adenocarcinoma NSCLCs could be differentiated from those with squamous cell carcinoma NSCLCs.2,3  Following promising pilot study results, a large-scale clinical trial is now under way to assess the use of breath-prints for postsurgical monitoring of lung cancer patients.4

Findings in Other Disease Sites

Gastric and lung cancers are not the only types of malignancy whose presence is evidenced by the chemicals in a patients' breath. Similar findings have also been reported in recent years for several other cancers and nonmalignant chronic diseases.

Not surprisingly, studies of lung disease have led the way. Researchers have reported the development of exhaled breath tests for lung cancer and inflammatory respiratory diseases like asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis, and respiratory tract infections, possibly including an on-the-spot tuberculosis (TB) test.5,6

“Pulmonary diseases seem to be characterized by a disease specific breath-print, as distinct profiles were found in patients with dissimilar diseases,” reported Kim DG van de Kant, MSc, Department of Pediatric Pulmonology, Maastricht University Medical Center, the Netherlands, and other coauthors of a systematic review of data from 73 controlled clinical trials of breath tests.5

One recent study even suggests that breath-prints can distinguish patients with Alzheimer's and Parkinson's disease from healthy control-group volunteers—and from one-another.7

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