Breast cancer is tied with lung cancer as the most prolific globally diagnosed cancer. The WHO estimates that there were 2.09 million cases of breast cancer in 2018.[1]According to the CDC, breast cancer has the highest rate of newly diagnosed cancer in women and is the second most lethal form of cancer among women.[2]It was estimated that in 2018 there was 206,670 new cases of breast cancer in the United States alone, representing 30% of all new cancer diagnoses in women.[3]In recent decades the survival rate for breast cancer has seen a dramatic increase, currently the average survival rate for all stages of breast cancer sits at a respectable 91%.[4] This is due to massive awareness campaigns and robust screening programs. While screening programs suchas regular mammograms and physical exams have increased the survival rates, they still maintaininherentflaws. Women with dense breast tissue are at a higher risk of developing breast cancer while simultaneously being more difficult to diagnose due to limitations of x-ray technology.[5]

 

The standard procedure for administering a mammogram can be uncomfortable for the patient and also have a high false positive rate with 67% sensitivity.[6]A more sensitive diagnostic procedure that could eliminate the high levels of false positives would reduce healthcare costs.It can also be extremely stressful for a patient who receives a false positive result as they await confirmation.[7]As such, there is need for a simple non-invasive breast cancer test that could be quickly scaled up to a national screening program. Breath analysis represents the best of both worlds; potentially providing a more sensitive screening test and a less invasive test for the patient.

Several proof of concept studies have successfully demonstrated breath analysis as a highly sensitive diagnostic tool for breast cancer.As with other cancer breath biomarker discovery trials, an exhaustive list of potential VOCs has been established.[8]A ground-breaking study by Phillips et al.tentatively identified 8 chemicals that were able to distinguish the breath ofbreast cancer patientsfrom healthy controlswith a sensitivity of 94.1% and 73.8% selectivity. While this study showed promising results, it made use of a costly gas-chromatography mass-spectrometry setup, which also requires extensive training to use.[9]Similar studies making use of GC-MS for breath analysis but using different target VOCs have also been successful in detecting breast cancer, but with lower sensitivity (72.7-78.5%). While these studies had lower sensitivity than Phillips et al. they have high specificity for breast cancer (88.3-91.7%).[10-11]
 

There has also been some success utilizing nanoparticle-based sensor arrays to detect breast cancer using exhaled breath.[12]However, this study featured a very small sample pool of cancer patients. There are also several limitations inherent to eNose technology that will need to be addressed over several years, possibly decades, before the technology becomes clinically useful. In the short term larger clinical trials are necessary to validate these clinical results. Additionally, alternative analytical techniques that are less expensive and require less training should be explored.

References

[1]Cancer https://www.who.int/news-room/fact-sheets/detail/cancer(accessed Jun 11, 2019).

[2]USCS Data Visualizations https://gis.cdc.gov/grasp/USCS/DataViz.html(accessed Jun 13, 2019).

[3]Siegel, R. L.; Miller, K. D.; Jemal, A. Cancer Statistics, 2018. CA: A Cancer Journal for Clinicians2018, 68(1), 7–30.https://doi.org/10.3322/caac.21442.

[4]de Groot, P. M.; Wu, C. C.; Carter, B. W.; Munden, R. F. The Epidemiology of Lung Cancer. Translational LungCancer Research2018, 7(3), 220-233–233.

[5]Boyd, N. F.; Guo, H.; Martin, L. J.; Sun, L.; Stone, J.; Fishell, E.; Jong, R. A.; Hislop, G.; Chiarelli, A.; Minkin, S.; et al. Mammographic Density and the Risk and Detection of Breast Cancer. New England Journal of Medicine2007, 356(3), 227–236. https://doi.org/10.1056/NEJMoa062790.

[6]Berg, W. A.; Gutierrez, L.; NessAiver, M. S.; Carter, W. B.; Bhargavan, M.; Lewis, R. S.; Ioffe, O. B. Diagnostic Accuracy ofMammography, Clinical Examination, US, and MR Imaging in Preoperative Assessment of Breast Cancer. Radiology2004, 233(3), 830–849. https://doi.org/10.1148/radiol.2333031484.

[7]Lindfors, K. K.; O’Connor, J.; Parker, R. A. False-Positive Screening Mammograms: Effect of Immediate versus Later Work-up on Patient Stress. Radiology2001, 218(1), 247–253. https://doi.org/10.1148/radiology.218.1.r01ja35247.

[8]Pereira, J.; Porto-Figueira, P.; Cavaco, C.; Taunk, K.; Rapole, S.; Dhakne, R.; Nagarajaram, H.; Câmara, J. S. Breath Analysis as a Potential and Non-Invasive Frontier in Disease Diagnosis: An Overview. Metabolites2015, 5(1), 3–55. https://doi.org/10.3390/metabo5010003.

[9]Phillips, M.; Cataneo, R. N.; Ditkoff, B. A.; Fisher, P.; Greenberg, J.; Gunawardena, R.; Kwon, C. S.; Rahbari-Oskoui, F.; Wong, C. Volatile Markers of Breast Cancer in the Breath. Breast J2003, 9(3), 184–191.[10]Phillips, M.; Cataneo, R. N.; Saunders, C.; Hope, P.; Schmitt, P.; Wai, J. Volatile Biomarkers in the Breath of Women with Breast Cancer. J Breath Res2010, 4(2), 026003. https://doi.org/10.1088/1752-7155/4/2/026003.

[11]Li, J.; Peng, Y.; Liu, Y.; Li, W.; Jin, Y.; Tang, Z.; Duan, Y. Investigation of Potential Breath Biomarkers for the Early Diagnosis of Breast Cancer Using Gas Chromatography-Mass Spectrometry. Clin. Chim. Acta2014, 436, 59–67. https://doi.org/10.1016/j.cca.2014.04.030.

[12]Shuster, G.; Gallimidi, Z.; Reiss, A. H.; Dovgolevsky, E.; Billan, S.; Abdah-Bortnyak, R.; Kuten, A.; Engel, A.; Shiban, A.; Tisch, U.; et al. Classification of Breast Cancer Precursors through Exhaled Breath. Breast Cancer Res. Treat.2011, 126(3), 791–796. https://doi.org/10.1007/s10549-010-1317-x.

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Breast Cancer

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