Optical imaging techniques have emerged as a possible alternative to predict pathological complete response (pCR) in breast cancer patients undergoing neoadjuvant chemotherapy (NAC). Our team developed a so-called diffuse optical tomographic breast imaging system (DOTBIS) which does not require the use of contrast agents or compression and enables imaging of the whole breast volume using low intensity near infrared light capable to measure tissue concentration of total hemoglobin (ctTHb). In this retrospective study, we evaluated 55 stage II-III BC patients in the neoadjuvant setting who received weekly paclitaxel x 12, followed by dose-dense adriamycin/cyclophosphamide every 2 weeks x 4. DOTBIS images were acquired from the patient whole breast volume at 6 different time points: at baseline (TP0); two weeks after the first taxane infusion (TP1); after four infusions of taxane (TP2); at the end of the taxane regimen and before starting AC cycle (TP3); after two AC infusions (TP4); and at the end of NAC and before surgery (TP5). In order to evaluate whether pCR status influences the change of ctTHb over time, we designed a multilevel mixed-effect model. pCR was defined as no invasive tumor cells from the breast and axillary tissue at surgery (ypT0 ypN0). Changes in ctTHb levels compared to baseline (TP0) values were statistically significant different between pCR (n = 20) and non-pCR (n=35) at all time points except at TP1 and at the end of the taxane cycle (TP3).