Abstract
<title>Abstract</title> <p>Background Progression of breast cancer is the result of a malignant epithelial cell and tumor-related microenvironment. This microenvironment involves stromal remodeling, vascular-like spaces, immune infiltration and proliferation. Immunohistochemistry giving clinically relevant information on the status of hormonal receptors (ER and PR/PGR), HER2, and Ki-67; however, the association of the biomarker profiles with the quantitative histological microenvironmental patterns is still incompletely explored. Objective To determine whether vascular-like morphology and stromal histomorphometric features in breast cancer H&E slides differ according to immunohistochemical biomarker status. Methods A secondary digital pathology analysis is proposed using public breast cancer histology datasets containing H&E slides and matched or corresponding immunohistochemistry data, particularly ACROBAT and IHC4BC. Vascular-like spaces and stromal regions were quantified from H&E images using image-processing and/or deep-learning segmentation. Results The features that were extracted included vessel-like density, vessel-like area fraction, mean vessel-like diameter, circularity, irregularity, stroma fraction, tumor-cell density, perivascular cellularity. These characteristics will be compared according to categories of ER, PR/PGR, HER2 and Ki-67. An exploratory Tumor Microenvironment Histology Index (TMHI) was created to summarize vascular-like and stromal remodeling. The proposal of a Phi Deviation Index materializes as a philosophical-morphometric descriptor of proportional imbalance across tumor, stroma, vascular-like, and cellular compartments. Conclusions This study may offer a clear framework for connecting routine H&E morphology with immunohistochemical biomarker patterns of clinical relevance. It is suggested with best breast cancer image analysis that we move away from just tumor detection, toward quantification of the tumor microenvironment. The Phi extension provides cancer with a philosophical definition as a disturbance of tissue proportion and spatial arrangements. It is explicitly exploratory, as well as empirically testable.</p>