Abstract P5-01-07: Oxyhemoglobin Flare after the First Day of Neoadjuvant Breast Cancer Chemotherapy Predicts Overall Response
Authors: Roblyer DM , Ueda S , Cerussi AE , Tanamai W , Durkin A , Mehta RS , Hsiang D , Butler J , Tromberg BJ. 
Published: April 2011

Abstract
Background: Breast cancer patients who do not respond to neoadjuvant chemotherapy undergo months of unwarranted side effects. Early, non-invasive markers of response would provide physicians a valuable tool to make evidence-based changes to treatment strategies. Methods: Diffuse Optical Spectroscopic Imaging (DOSI) was used to measure hemodynamic and metabolic information from tumors and surrounding normal tissue in 23 breast cancer patients undergoing neoadjuvant chemotherapy. DOSI uses temporally modulated near-infrared light to determine absolute tissue molar concentrations of oxyhemoglobin, deoxyhemoglobin, as well as water and lipid content and requires no exogenous contrast agent. Measurements are made using a simple handheld probe placed on the skin. Each measurement takes less than one minute and multiple measurements are made in a grid pattern over the tumor and surrounding normal areas of the breast. Functional images of the breast tissue are made and compared over sequential time points. Measurements were made before the start of treatment and during the first week after the first infusion. Patients received either doxorubicin + cyclophosphamide (AC) or paclitaxel + carboplatin at their first infusion. Overall response to therapy was determined by the decrease in anatomic tumor size. Results: A flare in tumoral oxyhemoglobin concentration occurred on day 1 after the start of chemotherapy in patients achieving a partial (PR) or pathologic complete response (pCR). Oxyhemoglobin concentration increased 44.5% (± 46.1% SD) in PR patients (n=11) and 41.4% (± 39.1% SD) in pCR patients (n=8) (see figure 1). Nonresponding (NR) patients (n=5) exhibited no oxyhemoglobin flare and an average decrease in concentration of -22.5% (± 5.10% SD) was observed on day 1. This flare was sufficient to perfectly discriminate non-responding patients from responding patients in this study cohort. Additionally, the spatial extend of elevated oxyhemoglobin over the anatomic tumor location increased during the flare. The oxyhemoglobin flare was observed in all responding patients regardless of specific chemotherapy regimen received, receptor status, age, tumor size and tumor grade.
Discussion: We have shown, in this patient cohort, that a non-invasive optical measure can discriminate non-responding tumors on the first day after the start of neoadjuvant breast cancer chemotherapy. The observed flare in oxyhemoglobin may be due to either decreased cellular metabolism and subsequent decrease in conversion of oxy to deoxyhemoglobin, or to a transient increase in perfusion to the tumor. Increased perfusion may be due to an acute inflammatory response, characterized by vessel dilation and increased vascular permeability, and triggered by tumor cell-damage. Future studies will confirm these initial findings and help to elucidate the biological causes of the observed oxyhemoglobin flare.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-01-07.