Baseline and Early-Delta Quantitative Ultrasound Radiomics for Predicting Pathologic Response to Neoadjuvant Chemotherapy in Breast Cancer

Background/Objectives: Early identification of breast cancer patients who are likely or unlikely to benefit from neoadjuvant chemotherapy (NAC) remains clinically important because ineffective treatment may delay definitive surgery and expose patients to unnecessary toxicity. Quantitative ultrasound (QUS) radiomics offers a contrast-free and repeatable method for extracting tissue-sensitive imaging biomarkers from raw ultrasound data. This study aimed to evaluate whether baseline QUS radiomic features and early treatment-induced changes could predict a pathologic response to NAC in a real-world single-center cohort. Methods: We designed a prospective observational study including 96 consecutive women with biopsy-proven stage II–III breast cancer treated with NAC at Victor Babes University of Medicine and Pharmacy Timisoara. All patients underwent standardized QUS examinations before treatment and again at week 2. The response was defined pathologically at surgery as residual cancer burden class 0/I versus II/III. Clinical, histopathologic, and QUS variables were compared between responders and non-responders. Group comparisons used Student’s t test, Mann–Whitney U test, chi-square testing, and Fisher’s exact test where appropriate. Multivariable logistic regression was used to identify independent predictors of response. Model discrimination was summarized using the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy. Results: Forty-three patients (44.8%) were classified as responders and 53 (55.2%) as non-responders. Responders had higher baseline Ki-67 values (47.8 ± 13.1% vs. 41.9 ± 13.0%, p = 0.033), lower baseline homogeneity (0.3 ± 0.1 vs. 0.4 ± 0.1, p = 0.010), and higher peritumoral heterogeneity (0.9 ± 0.1 vs. 0.8 ± 0.2, p = 0.027). At week 2, responders showed larger increases in mid-band fit (3.0 ± 0.8 vs. 1.2 ± 0.8 dB, p < 0.001), greater entropy change (0.7 ± 0.2 vs. 0.2 ± 0.2, p < 0.001), more pronounced spectral intercept reduction (−3.5 ± 1.4 vs. −1.2 ± 1.3, p < 0.001), and greater tumor shrinkage (−24.3 ± 7.0% vs. −11.1 ± 5.7%, p < 0.001). In multivariable analysis, Δ MBF and Δ entropy remained independent predictors of pathologic response. The combined clinical-plus-QUS model achieved an AUC of 0.89. Conclusions: Baseline microstructural heterogeneity and very early QUS-derived treatment changes were strongly associated with the pathologic response to NAC. These findings support the potential role of QUS radiomics as a low-cost, repeatable early-response biomarker in breast cancer.