We have introduced working technology that provides for time–series imaging of the hemoglobin signal in large tissue structures. In this study we have explored our ability to detect aberrant time–frequency responses of breast vasculature in subjects with Stage II breast cancer, at rest and in response to simple provocations. The hypothesis being explored is that time–series imaging will be sensitive to the known structural and functional malformations of the tumor vasculature. Mammographic studies were conducted using an adjustable hemispheric measuring head containing 21 source and 21 detector locations (for 441 source–detector channels). Simultaneous dual–wavelength (760 and 830 nm) studies were performed on women lying prone with the breast hanging in a pendant position. Two classes of measure were performed: 1) 20-minute baseline measurements wherein the subject was at rest; 2) provocation studies wherein the subject was asked to perform some simple breathing maneuvers. Collected data were analyzed to identify the central tendencies and time–frequency structure of the detector responses, and those of the image time series. Image data were generated using the Normalized Difference Method [Pei et al., Appl. Opt. 40, 5755–5769 (2001)]. Results obtained clearly document three classes of dynamic anomaly in the tumor–bearing breast relative to the healthy contralateral breast. First, breast tumors exhibit oxygen supply/demand imbalance in response to an oxidative challenge (breath hold). Second, the vasomotor response of the tumor vasculature is mainly depressed and exhibits an altered modulation. Third, the region of the breast wherein the altered vasomotor signature is seen extends well beyond the margins of the tumor itself.