Early alterations in textural characteristics of quantitative ultrasound spectral parametric maps, in conjunction with changes in their mean values, are demonstrated here, for the first time, to be capable of predicting ultimate clinical/pathologic responses of breast cancer patients to chemotherapy. Mechanisms of cell death, induced by chemotherapy within tumor, introduce morphological alterations in cancerous cells, resulting in measurable changes in tissue echogenicity. We have demonstrated that the development of such changes is reflected in early alterations in textural characteristics of quantitative ultrasound spectral parametric maps, followed by consequent changes in their mean values. The spectral/textural biomarkers derived on this basis have been demonstrated as non-invasive surrogates of breast cancer chemotherapy response. Particularly, spectral biomarkers sensitive to the size and concentration of acoustic scatterers could predict treatment response of patients with up to 80% of sensitivity and specificity (p=0.050), after one week within 3-4 months of chemotherapy. However, textural biomarkers characterizing heterogeneities in distribution of acoustic scatterers, could differentiate between treatment responding and non-responding patients with up to 100% sensitivity and 93% specificity (p=0.002). Such early prediction permits offering effective alternatives to standard treatment, or switching to a salvage therapy, for refractory patients.