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Background: Near-infrared optical measurements have been recently shown to offer a promising non-invasive way for monitoring breast neoadjuvant chemotherapy (NAC) and predicting outcome. In particular, snapshots of tissue oxy and deoxy-hemoglobin concentration as well as water and lipid content have been demonstrated to be sensitive to therapy-induced changes. In this study, we extend optical measurements to capture additional hemodynamic and metabolic biomarkers revealed by dynamically imaging breast tissue during fractional mammographic compression. Using our dynamic tomographic optical breast imaging (TOBI) system we evaluate the early prediction performance of this advanced technology. Methods: We are conducting a pilot feasibility study in female patients with unilateral locally advanced breast cancer undergoing standard-of-care NAC. Pre-treatment and day 7 post-treatment TOBI scans are obtained, with additional (optional) scans on day 1 of each subsequent chemotherapy cycle. Both breasts are compressed in turn to 4-8 lbs of force, and optical images are acquired once every 2 seconds over two minutes. Time-resolved oxy-(HbO), deoxy-(HbR), and total-(HbT) hemoglobin concentration and hemoglobin oxygen saturation (SO2) are calculated. The compression-induced rate of change of HbT correlates with changes in tissue blood volume indicative of biomechanical properties. The evolution of tissue SO2 is modeled to obtain an index of the ratio of oxygen metabolism to blood flow. Therapy induced changes are quantified, and comparisons between changes in responders vs. non-responders are performed (response is defined here as >50% reduction in the largest tumor diameter). Results: We have enrolled 20 patients so far, of which 90% (N = 18) completed both the day 0 and day 7 scans. 17 patients have undergone surgery at this point. We focused our initial analysis on 5 HER2+ patients, of which two were non-responders, and three were responders according to our criteria. Four patients received taxol+herceptin+lapatinib, while the other received taxol+lapatinib only. In this small subgroup, the non-responders had an average increase of 1% in total hemoglobin concentration (HbT) from day 0 to day 7, while the responders had an average 12% decrease in HbT, respectively. We also noted different trends in the evolution of the tissue oxygen consumption to blood flow ratio, which increased 32% in non-responders from day 0 to day 7, while decreasing 11% in responders. Conclusions: The large percentage of enrolled patients that completed both initial scans demonstrates the feasibility of using dynamic optical breast tomography for breast neoadjuvant chemotherapy monitoring. Results in a small cohort of 5 HER2+ patients suggested a decreasing trend in HbT for responders as observed by previous studies. We also report for the first time an increase in the metabolic ratio of oxygen consumption to blood flow in non-responders vs. a decrease in responders. These initial results of our on- going study suggest that dynamic TOBI can detect changes due to treatment and may have predictive value for the treatment outcome and supports further studies of this non- invasive and portable tool for chemotherapy monitoring. [ABSTRACT FROM AUTHOR]

Introduction: Population based studies (eg, Hershman et al. BCRT 2006 and Lohrisch et al. JCO 2006) showed poorer survival associated with long delays in adjuvant chemotherapy (CTX) initiation following definitive surgery (DS) for women with breast cancer (BC). Delays in CTX following diagnosis (DX) have not been evaluated. The ASCO/NCCN quality measures (QMs) recommend CTX <=120 days after DX for patients with stage II/III ER/PR negative disease. We sought to examine the impact of delayed CTX on survival overall and stratified by disease-specific prognostic factors. Methods: 4,608 women with stage I-III HER2 negative breast cancer diagnosed between 2000 and 2006 at 8 NCCN centers were identified using the NCCN outcomes database. Patients with T3/4 disease or who received neoadjuvant therapy were excluded. The association between CTX timing and OS was evaluated using multivariate Cox models adjusted for CTX type, age, race, BMI, residential distance, insurance, SES, comorbidity, ER/PR, LVI, grade, T stage, and N stage. The impact of CTX timing was evaluated using a >90-day (d) DS-to-CTX threshold, based on poor outcomes observed in prior studies, and a >120d DX-to-CTX threshold, based on the ASCO/NCCN QMs. Results: Median follow-up was 7.2 years and OS at 7 years was 89%. Overall, 401 (8.7%) patients received CTX >120d after DX and 113 (2.4%) patients received CTX >90d after DS. The DX-to-CTX interval was more strongly correlated with the DX-to-DS (r = 0.74) interval than DS-to-CTX (r = 0.54) interval. A >90d DS-to-CTX interval was significantly associated with poorer survival (HR: 1.65, 95% CI 1.04-2.60, p = 0.03) in adjusted analyses. Shorter DS-to-CTX thresholds of >60d (n = 636, HR: 1.13, 95% CI: 0.89-1.43, p = 0.319) or >75d (n = 273, HR: 1.05, 95% CI 0.74-1.49, p = 0.76) were not associated with OS. The association between a >120d DX-to-CTX interval and OS was not statistically significant (HR: 1.32, 95% CI 0.99-1.76, p = 0.06). Patients who received CTX >135d(n = 231, HR1.25, 95% CI: 0.87-1.81, p = 0.22)or>150d(n = 128, HR1.15, 95% CI: 0.59-2.24, p = 0.69) after DX did not display an increased risk of death. Excluding pathological staging factors from the model had no effect on the results. In subgroup analyses stratified by ER/PR, LVI, grade, T stage or N stage, a >120d delay in CTX did not display significant associations with OS. Among ER/PR negative patients, the association between a >120d delay and OS was borderline non-significant after adjusting the p-value for multiple hypothesis testing using the false discovery rate method (HR: 1.80, 95% CI: 1.16-2.79, p = 0.09). Conclusion: Consistent with previous studies, CTX delays of >90 days following surgery were associated with poorer survival. OS was not significantly compromised in patients with DX-to-CTX intervals >120 days although this analysis may have limited power to detect small effects. More variation in the DX-to-CTX interval was attributed to pre-surgery time which may explain the differences observed between the DX-to-CTX and DS-to-CTX intervals. Among patients with ER/PR negative disease, a non-significant association between OS and a >120 day DX-to -CTX interval was observed that warrants further examination. [ABSTRACT FROM AUTHOR]