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Tumor Discovery Volatile organic compounds for cancer screening

body’s metabolism, creating unique patterns in the VOCs When diagnosed early, breast cancer is often curable.
being produced and released. Unique VOC profiles have Improved breast cancer screening and early detection are
demonstrated diagnostic utility for several benign and associated with improved prognosis and decreased health-
malignant conditions, enabling prediction of disease care costs. Studies exploring barriers to breast cancer
burden and response to treatment. 1-6 screening report a combination of social, geographic,

Conditions with similar pathophysiological processes and economic factors. 12-17 Social factors, well described in
often exhibit similar VOC patterns (i.e., ulcerative the literature, include health literacy, perceived physical
colitis, Crohn’s disease, and irritable bowel syndrome are and emotional discomfort associated with a breast
inflammatory gastrointestinal [GI] conditions that produce examination and mammography and cultural and religious
1,3
similar VOC spectrums). As such, a single VOC cannot considerations. 13,15,17 Geographic and socioeconomic
discriminate between such disease processes. Rather, factors include disparities in access to screening services
13-16
patterns of several measured VOCs have been utilized to for breast cancer. There is an ongoing global need to
describe distinct profiles, which have been demonstrated develop inexpensive screening tests that are safe, effective,
in proof-of-concept clinical studies to be sensitive and and improve patient experience. Breath analysis represents
specific for the diagnosis of several important diseases, a minimally invasive point-of-care tool allowing for early
including malignancies. Thus, VOC profiles represent cancer detection that is inexpensive and accessible. This
1-5
promising oncologic biomarkers. technology may increase compliance with screening and
improve access to cancer care globally.
Breath analysis of exhaled VOCs is emerging as a
non-invasive method for early cancer diagnosis. Exhaled Analysis of over 1.8 million screening mammograms in
breath is non-invasively accessible, inexpensive to sample, the United States between 2004 and 2008 in women between
associated with increased patient compliance, and yields 18 and 80 years of age reported a sensitivity of 84.4% and
1-4
samples that are easily analyzed, stored, and transported. a specificity of 90.8%. The recall rate was 9.6%, with a
10
Serial testing is both safe and feasible. Exhaled breath VOC positive predictive value of 4.3 (Figure 1). In contrast,
12
analysis has the potential to be widely implemented as a in a small case–control study, Phillips et al. reported a
simple point-of-care tool providing concurrent screening 93.8% sensitivity and 84.6% specificity in predicting the
for a wide range of cancers. In addition, this technology presence of breast cancer with biopsy-proven breast cancer
may facilitate treatment response monitoring and post- using a prediction model with five VOCs in exhaled breath
treatment cancer surveillance. (Figure 2). This small case–control study (n = 101, with
51 patients with breast cancer) supports the potential for
2. Breast cancer accurate breast cancer diagnosis using a pattern of five
exhaled VOCs (1-phenylethanone, 2.3-dihydro-1-phenyl-
With over 2.3 million cases and 685,000 deaths worldwide 4(1H)-quinazolinone, 2-propanol, heptanal, and isopropyl
in 2020, breast cancer is the second most diagnosed myristate) identified through gas chromatography (GC)/
malignancy. It remains the leading cause of cancer-related mass spectroscopy (MS). 12
7,8
death in women. At present, mammography is the gold-
7-9
18
standard modality for the early detection of breast cancer, Patterson et al. analyzed 308 VOCs in 20 patients with
detecting cancer 1.5 – 4 years before the disease becoming breast cancer and 20 healthy controls, using aggregate low-
clinically detectable. 10 dimensional summaries and compound quantity clustering
to predict a diagnosis of breast cancer with a sensitivity
The impact of early, effective screening has been well 19
established. A seminal study by Tabár et al. demonstrated of 72% and a specificity of 64%. Similarly, Phillips et al.
11
employed c-statistics to identify the predictive value of
that women aged 40 – 69 participating in breast cancer individual VOCs to identify potential breast cancer
screening benefit significantly from earlier intervention
with decreased morbidity and mortality, compared to biomarkers in exhaled breath. Monte Carlo simulations
women who did not participate in screening programs. were then used to select the chromatographic time slices
Patients participating in organized mammography that identified breast cancer with better-than-random
screening have a 60% lower risk of breast cancer-related accuracy. The VOCs with the highest predictive values were
mortality within 10 years of diagnosis. The importance of identified. A multivariate algorithm using a combination
timely access and compliance with breast cancer screening of >30 VOCs comparing 54 women with breast cancer and
is highlighted by the increased morbidity and mortality 204 cancer-free controls revealed a sensitivity of 78.5%, a
of breast cancer in developing countries, where a delayed specificity of 88.3%, and a c-statistic of 0.89.
diagnosis is associated with worse outcomes compared to Li et al. validated a predictive model using four
20
high- and middle-income countries. 8 biomarkers for breast cancer in exhaled breath (hexanal,

Volume 3 Issue 2 (2024) 3 doi: 10.36922/td.2061