Fig. 1

Overview of the experimental design and representative H&E and IHC images of clinical samples. (a) Breast cancer patient samples were collected through needle biopsies prior to neoadjuvant chemotherapy and from surgical resections. FFPE sections were pathologically reviewed to confirm TNAC diagnosis. Normal, DCIS, and invasive tumor regions were dissected for mass spectrometry (MS)-based proteomic profiling, with selected samples also subjected to whole-exome sequencing (WES). Bioinformatic analyses were conducted to identify dysregulated proteins, altered pathways, and potential mechanisms underlying tumor progression and chemoresistance. Our findings support the rationale for chemotherapy de-escalation and highlight the potential utility of targeted therapies such as PI3K inhibitors. (b) Immunohistochemical (IHC) staining of Ki67, HER2 (ERBB2), EGFR, and AR in normal, DCIS, and invasive TNAC tissues. Scale bar = 50 μm. (c) Representative H&E-stained images of normal breast tissue, TNAC DCIS, TNAC invasive carcinoma, and NA-TNBC invasive carcinoma. Scale bar = 50 μm. (d) Principal component analysis (PCA) clustering shows a clear separation of normal, DCIS, and invasive TNAC tissues, indicating distinct molecular profiles. (e) Boxplots displaying MS-based expression levels of EGFR (top) and HER2/ERBB2 (bottom) across normal, DCIS, and invasive TNAC tissues (*p < 0.05).