Neoadjuvant chemotherapy is the choice of treatment in LABC. 3-step-PCA was employed for data analysis and the 3rd step gave two groups of tissues which were histopathologically correlated to tissues with and without residual tumor i.e., negative and positive response, respectively. The mean spectra of tissues with residual tumor exhibit very high protein content (δCH2 at 1450 cm-1, broad amide I and III, low 1450/amide I) and spectra of without tumor tissues show lipid predominance (δCH2 at 1440 cm-1, broad amide I and III and high 1440/amide I). Mean spectra also exhibit signatures (1240 and 1270 cm-1) of fibrous proteins like collagen which suggest chemotherapy-induced-fibrosis. These results indicate the feasibility of Raman spectroscopic assessment tumor response to neoadjuvant chemotherapy in breast cancers. Prospective rigorous validation and fabrication of suitable fibreprobes, on-line Raman spectroscopic approaches during surgical procedures/less invasive needle biopsy can certainly improve breast conservative treatment following neoadjuvant therapy