Diagnostic Efficiency of Serum-Based Infrared Spectroscopy in Detecting Breast Cancer

A Meta-Analysis

Louise Julie Pabico, BS Bio; Jennica Naiomi Jaron, BS Bio; Marc Erickson Mosqueda, BS Bio; Jorge Jaesen Wu, BS Bio; Raphael Enrique Tiongco, RMT, MSMT; Pia Marie Albano, RMT, MSc, PhD


Lab Med. 2023;54(1):98-105. 

In This Article

Abstract and Introduction


Background: The advancement of Fourier transform infrared (FTIR) spectroscopy as a potential diagnostic tool in the clinical setting has been studied over the years, particularly its application in cancer diagnostics.

Objective: To summarize previous research on FTIR spectroscopy in detecting breast cancer using serum specimens.

Methods: Related literature was searched and screened from various databases. Relevant data were then extracted, tabulated, and analyzed using Meta-DiSc 1.4 software.

Results: Sensitivity and specificity rates were 90% to 100% and 80% to 95%, respectively. The area under the receiver operating characteristic curve was at 0.9729, indicating that serum analysis via FTIR spectroscopy can accurately discriminate between healthy individuals and patients with breast cancer.

Conclusion: Overall, FTIR spectroscopy for breast cancer diagnosis using serum specimens shows promising results. However, further studies are still needed to validate these claims.


Breast cancer is one of the most prevalent cancers and the principal cause of cancer-related deaths in women worldwide,[1] with an estimated 2 million cases in 2018.[2] Statistical analyses of the past breast cancer trends in women showed an increasing rate of global burden in terms of incidence and mortality in 102 countries in the past 26 years (1990–2016). We expect that the incidence and mortality rates will escalate further in the succeeding years. Further, these rates are higher in well-developed countries, whereas developing countries have lower incidence with higher mortality rates, which is partly attributed to the lack of breast cancer screening.[3–5]

Mammography is a noninvasive and inexpensive screening method for breast cancer with good sensitivity (63%–98%) with increasing age.[6] However, there have been reports of less-than-optimal values (~30%–48%) in women with dense breasts.[7,8] Further, a triple assessment, which entails multiple tests such as clinical examination, mammography, and ultrasound, has been found to have high sensitivity, specificity, and concordance values. Although ultrasound and MRI are sensitive in detecting invasive breast cancers, the 2 methods also risk overestimating tumor extent.[9] Also, false-positive and false-negative results may occur, especially in young, premenopausal women.[10] Hence, early breast cancer testing in high-risk groups demands new strategies.

Fourier transform infrared (FTIR) spectroscopy is an analytical technique used to characterize solids, liquids, and gases[11] used in organic, inorganic, or polymeric materials.[12,13] An FTIR spectrometer uses an interferometer that merges 2 or more light sources to create an interference pattern that can be measured and analyzed. The infrared light goes from the glowing source to a beam splitter usually made of polished KBr crystal placed at a 45-degree angle. The Fourier standard computer algorithm converts the interferogram from a time domain into a frequency domain spectrum that allows people to see the strength of absorption as a function of the frequency (or wavelength). The FTIR can also be enhanced with various accessories to fit the specific requirements for specimen analysis, such as ATR (attenuated total reflection), transflection, and transmission mode. An infrared spectrum results from this technique, regardless of the accessories used.[14]

FTIR spectroscopy can detect biochemical compositions such as nucleic acids, proteins, lipids, and carbohydrates by identifying molecular conformations, bonding types, functional groups, and intermolecular interactions. The technique has gained increased interest over the years because it is versatile in detecting biochemical and biological features of specimens. Infrared spectroscopy produces a signature spectral fingerprint based on the absorbance ratios from the specimens. The intensities and positions of peaks depend on the biochemical compositions of a specimen,[15] which may be used to differentiate cell types. It has been used to compare healthy vs cancerous or diseased conditions and even detect degree of tumor aggression.[16] Therefore, FTIR spectroscopy has been recognized as an emerging tool in diagnostics because it can provide pertinent information on patient health status.

Several studies have been published on FTIR spectroscopy that use human blood specimens for disease screening and diagnosis. High-throughput ATR-FTIR spectroscopy has been shown to be capable of delivering a diagnosis within minutes using blood specimens. Blood collection is a relatively simpler method than mammography and CT scans,[17] and the serum is used in routine clinical tests to carry information regarding intra- and extracellular events. Serum is the liquid part of blood that contains no clotting factors or blood cells; it is the most complex biofluid, with more than 20,000 different proteins.[16] Blood perfuses to organs throughout the human body, gaining proteomes from neighboring cells and organs. The peptidome is a component of blood that is thought to have cancer-specific diagnostic information and is abundant in serum.[15] Previously established biomarkers used in aiding breast cancer diagnosis, such as the carbohydrate antigen (CA) 549, CA M26, CA M29, CA 15–3, and the carcinoembryonic antigen (CEA), are also found in serum.[18]

In this study we synthesized the existing literature on the potential of FTIR spectroscopy in detecting breast cancer using serum. The sensitivity, specificity, likelihood ratios (LRs), diagnostic odds ratios (DORs), and area under the curve (AUC) of spectral analysis to diagnose breast cancer were compared to the current criterion standard, which is the microscopic examination of H&E-stained biopsy specimens.