Monitoring tumor response to therapy can enable assessment of treatment efficacy, maximizing patient outcome and survival. We employ a noninvasive, handheld laser breast scanner (LBS) based on broadband diffuse optical spectroscopy (DOS) in conjunction with contrast-enhanced magnetic resonance imaging (cMRI) to assess tumor response to presurgical neoadjuvant chemotherapy. DOS and cMRI scans are performed after the first and fourth cycles of a doxorubicin/cyclophosphamide regimen in a patient with invasive ductal carcinoma. DOS measurements are used to quantify bulk tissue optical and physiological parameters, which are mapped to - and -weighted cMRI images. Initial DOS measurements show high tumor/normal contrast in total hemoglobin concentration (THC, versus ) and water fraction ( versus ) colocalized with regions of strongly enhancing -wieghted and cMRI signals. After the fourth cycle of chemotherapy, we observe decreases in peak MRI contrast-enhancement values (37.6%) and apparent lesion volume (21.9 versus ), which corresponds to physiological changes measured by DOS, including a 20 to 25% reduction in the spatial extent of the tumor and a 38.7% drop in mean total hemoglobin content (THC, 41.6 versus ). These data provide in vivo validation of the accuracy of broadband DOS and the sensitivity of optical methods to changes in tumor physiology.