A Network-Based Biomarker of Morphological Disruption Associated with Breast Cancer Malignancy

RESUMO

Breast cancer diagnosis commonly considers individual nuclear morphological characteristics, whereas their joint organization is less frequently evaluated. We developed the Morphological Network Disruption Index (MNDI), a patient-level measure of morphological abnormality relative to a benign reference state. Using the Wisconsin Diagnostic Breast Cancer dataset, ten nuclear characteristics were represented as network nodes, with MNDI summarizing disruption across 45 pairwise feature configurations. Performance was evaluated using repeated stratified five-fold cross-validation. Malignant lesions exhibited substantially higher MNDI than benign lesions (mean: 3.454 vs. 1.165; p = 2.94e-69). MNDI achieved an AUC of 0.941 (95% CI: 0.918-0.961), with 85.9% sensitivity and 91.6% specificity. A classifier using network-derived descriptors achieved an AUC of AUC of 0.928 +/- 0.024. Independent evaluation in the BreaKHis histopathology cohort showed limited discrimination (AUC = 0.538, 95% CI: 0.401-0.668), indicating dependence on the underlying morphological representation. MNDI provides an interpretable framework for quantifying patient-specific morphological disruption, while individual implementations require validation within compatible feature spaces.