Abstract Attenuated Total Reflection Fourier-Transform Infrared (ATR-FTIR) spectroscopy offers a promising, minimally invasive, and label-free approach for serum analysis, capable of detecting molecular-level changes associated with breast cancer (BC). Few studies have examined the use of Infrared (IR) spectroscopy to monitor BC progression, and correlations between specific spectral changes and tumor development remain underexplored. This study provides results from a technique that uses ATR-FTIR spectroscopy of blood serum, combined with curve fitting analysis to identify molecular changes in five spectral biomarkers (SBMs) linked with BC progression across tumor stages. These include increases in β-sheet structures (1536 cm-1) and disordered protein structures (1558 cm-1), and a decrease in α-helix (1547 cm-1), PO2 - asymmetric stretching (1062 cm-1), and C-O stretching of glycogen (1050 cm-1). These SBMs showed statistically significant differences (p 0.05 to p 0.0001) between healthy controls (HC) and also between different BC Groups classified by tumor size. Among them, the β-sheet (1536 cm-1), α-helix (1547 cm-1), and PO2 - asymmetric stretch (1062 cm-1) SBMs demonstrated high diagnostic performance, each achieving 93% sensitivity and 100% specificity. These findings highlight utility of specific SBMs for monitoring BC and suggest that IR-spectroscopy in combination with curve fitting technique could serve as a robust approach for differentiating BC severity levels based on tumor size. Citation Format: M. T. K. Vithanage, S. H. Ekanayake, H. Ghimire, M. K. Dayananda, G. Qin, R. Aneja, E. A. Janssen, A. G. Unil Perera. Attenuated Total Reflectance-Fourier Transform Infrared spectroscopy for monitoring biochemical changes in breast cancer serum across tumor stages abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-06-09.
Vithanage et al. (Tue,) studied this question.
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