Explorative Detection of Fractional Exhaled Nitric Oxide ( FeNO ) in Exhaled Breath of Patients With Breast Cancer

ABSTRACT Background Nitric oxide (NO), a gaseous messenger with pleiotropic functions, plays a role in cancer, including breast cancer (BC). Considering the high permeability and leakiness of NO across tissues and the increased levels of NO recently reported in exhaled breath and blood of patients with lung cancer, we explored exhaled NO levels in patients with BC in a future perspective of non‐invasive cancer detection. Patients and Methods Fractional exhaled NO (FeNO) levels were detected in the breath of 192 women with BC and malignancy‐free controls employing a widely used point‐of‐care (POC)‐based system previously developed for asthma monitoring. Results FeNO levels were lower in BC patients compared to controls, with the lowest levels in women with HER2‐expressing tumors. In univariate and multivariate analyses and after adjustment for age, smoking, and asthma, this difference was not significant. The effects of smoking were not statistically significant, whereas asthmatic subjects had significantly higher levels of FeNO ( p  = 0.006). Neither menopause nor BMI had a significant impact on FeNO levels. Conclusion Our explorative work indicates that FeNO levels are heterogeneously detected in the breath of BC patients in the absence of confounding effects and are associated with the clinical characteristics of the disease. More sensitive detection of exhaled NO and larger cohorts enriched with ER negative BC are needed to further explore the potential of NO in non‐invasive detection of BC, either alone or in conjunction with other BC‐related volatile markers, and extending the NO measurement to blood or tissues.