Tissue hemoglobin oxygen saturation (i.e., oxygenation) is a functional imaging endpoint that can reveal variations in tissue hypoxia, which may be predictive of pathologic response in subjects undergoing neoadjuvant chemotherapy. In this study, we used diffuse optical spectroscopic imaging (DOSI) to measure concentrations of oxyhemoglobin (ctO(2)Hb), deoxy-hemoglobin (ctHHb), total Hb (ctTHb = ctO(2)Hb + ctHHb), and oxygen saturation (stO(2) = ctO(2)Hb/ctTHb) in tumor and contralateral normal tissue from 41 patients with locally advanced primary breast cancer. Measurements were acquired before the start of neoadjuvant chemotherapy. Optically derived parameters were analyzed separately and in combination with clinical biomarkers to evaluate correlations with pathologic response. Discriminant analysis was conducted to determine the ability of optical and clinical biomarkers to classify subjects into response groups. Twelve (28.6%) of 42 tumors achieved pathologic complete response (pCR) and 30 (71.4%) were non-pCR. Tumor measurements in pCR subjects had higher stO(2) levels (median 77.8%) than those in non-pCR individuals (median 72.3%, P = 0.01). There were no significant differences in baseline ctO(2)Hb, ctHHb, and ctTHb between response groups. An optimal tumor oxygenation threshold of stO(2) = 76.7% was determined for pCR versus non-pCR (sensitivity = 75.0%, specificity = 73.3%). Multivariate discriminant analysis combining estrogen receptor staining and stO(2) further improved the classification of pCR versus non-pCR (sensitivity = 100%, specificity = 85.7%). These results show that elevated baseline tumor stO(2) are correlated with a pCR. Noninvasive DOSI scans combined with histopathology subtyping may aid in stratification of individual patients with breast cancer before neoadjuvant chemotherapy.
©2012 AACR.