As a group, breath tests to detect cancer have a relatively high level of sensitivity and specificity, despite the fact that they are still only in experimental stages of development. This is the conclusion from a new meta-analysis of early trials of the concept.

A breath test detects and quantifies preidentified, named volatile organic compounds (VOCs) within an exhaled breath to diagnose cancer, explain the study authors, led by George Hanna, MD, a surgeon at the Imperial College London in the United Kingdom.

The approach is still relatively immature and under development by multiple teams in oncology. "There are currently no breath tests used in oncology of cancer screening," Hanna told.

However, the concept is already in use in other areas of clinical practice, including breathalyzer devices for ethanol detection, carbon 13 urea breath testing for Helicobacter pylori, and exhaled nitric oxide testing in asthma.

In the new analysis, Hanna and colleagues identified 63 studies, all of which were phase 1 biomarker trials. They report that the studies showed that for cancer diagnosis, the mean (SE) area under the ROC curve for breath VOC analysis was 0.94 (0.01). The team also reports a pooled sensitivity of 79% (95% confidence interval [CI], 77% – 81%), and a pooled specificity of 89% (95% CI, 88% – 90%).

Big Steps Underway, Especially in the UK

Van Berkel also reported that he and colleagues are in the midst of securing funding for a large, multicenter trial of their breath test technology, which uses carbonyl cancer markers, to diagnose lung cancer. Their team has reported preliminary results with the test.

Diagnostic accuracy of a breath test to detect cancer

A confirmatory prospective study has been planned to determine the diagnostic accuracy of a breath test to detect cancer in an enriched population of about 18,000 patients referred from primary care for rapid assessment for esophageal and gastric cancers, in accordance to guidelines from the UK's National Institute for Health and Care Excellence.

"We have also established the framework for standardization and quality control measures for breath analysis, which have traditionally been barriers to the wider adoption of breath testing in clinical practice," he said.

It is unclear how breath tests may be ultimately used in oncology. In their article, Hanna and coauthors review the possibilities. First, an exhaled breath test could act as a triage investigation to direct patients who present with common nonspecific symptoms that could indicate cancer to have invasive or more specialized investigations, they noted.

Second, breath tests may have a role in screening programs (provided they are accurate enough). The noninvasive nature of the test and its acceptability by patients and practitioners would increase the uptake of screening, they add. Third, breath tests may have a role in monitoring the response to cancer therapy and in detecting disease recurrence, the meta-analysis coauthors believe.

"My concern with this review is that it takes a bunch of very different tests, looking at different volatile compounds in different cancers via different mechanisms, and lumps all the results together for an overall sensitivity and specificity. I am not sure what to conclude from those results," he told.