Breast cancer continues to be a leading cause of cancer death among women worldwide, necessitating practical early-detection methods. This study evaluates whole blood Raman spectroscopy for detection of malignancy-associated protein modifications and explore the relationship between these modifications and serum HER2 levels. This study involved Raman spectra and was performed across 27 (stages II-IV) breast cancer patients and 20 healthy subjects for the tests purpose (785 nm excitation). Welch's t-test, ROC analysis and PCA were performed to analyze eight protein-associated regions. For the eight Raman bands, seven of them had significant upward shifts in patients compared to controls (P<0.0001). Among this population, the bands at 1139 cm and 1346 cm achieved classification with perfect area under the curve (AUC 1.000, 100% sensitivity/specificity), whereas both the band at 1246 cm also showed an AUC of 1.000 and the band at 1285 cm had a corresponding AUC of 0.905 (90% specificity). The concentration of serum HER2 is significantly elevated in patients (p=0.0023) and correlated moderately with multiple spectral bands. PCA showed clear separation between the groups, with PC1 raspectively explaining 59.16% of the variation: Thase results suggest that whole- blood Raman spectroscopy detect coupled protein conformational changes in breast cancer, therefore defining the 1139, 1346, 1246 and 1285 cm bands as possible spectroscopic candidates. The method shows promise as a rapid, non-invasive liquid biopsy technique, particularly in low-resource settings, Collectively shows high classification accuracy within this small sample set: thorough evaluation and confirmation prior to clinical translation in larger independent cohorts free from systemic therapy is considerable importance.