A clinical study was undertaken investigating the efficacy of ultrasound to quantify cell death in tumor responses with cancer treatment. Patients (n = 25) with locally advanced breast cancer received anthracyline and taxane-based chemotherapy treatments over four to six months. The majority of patients went on to have a modified radical mastectomy and correlative whole mount histopathology. Data collection was carried out using an Ultrasonix-RP and an L15-5 6 cm transducer pulsed at 10 MHz with RF data collected five times during neoadjuvant chemotherapy. Data indicated increases of approximately 9 dBr (+/−1.67) maximally in ultrasound backscatter in patients who clinically responded to treatment. Patients assessed as responding poorly demonstrated significantly lower increases (2.3 +/− 1.7 dBr). Increases in 0-MHz intercept followed similar trends while increases in spectral slope were observed locally from tumor regions demonstrating increases in tissue echogenicity. This study demonstrates the potenti...