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Optical imaging of breast cancer oxyhemoglobin flare correlates with neoadjuvant chemotherapy response one day after starting treatment

Abstract
An increasing number of patients diagnosed with locally advanced breast cancer undergo preoperative neoadjuvant chemotherapy (NAC). Although disease-free and overall survival is approximately identical compared with postoperative therapy, primary NAC has been shown to downstage tumor grade and reduce tumor volume, leading to more breast-conserving surgeries. Patients who experience a pathological complete response (pCR) are associated with longer disease-free and overall survival. Unfortunately, between 8% and 20% of patients will have no clinical or pathologic response and will not benefit from months of treatment. Noninvasive markers to predict response very early during therapy would help physicians make evidencebased changes to treatment strategies, potentially minimizing side effects and maximizing therapeutic outcome.

Most clinical and imaging measures of response are obtained several weeks after the start of therapy. Here, we report that functional hemodynamic and metabolic information acquired using a noninvasive optical imaging method on the first day after neoadjuvant chemotherapy treatment can discriminate nonresponding from responding patients. Diffuse optical spectroscopic imaging (LAMMP TRD-5) was used to measure absolute concentrations of oxyhemoglobin, deoxyhemoglobin, water, and lipid in tumor and normal breast tissue of 24 tumors in 23 patients with untreated primary breast cancer. Measurements were made before chemotherapy, on day 1 after the first infusion, and frequently during the first week of therapy. Various multidrug, multicycle regimens were used to treat patients. Diffuse optical spectroscopic imaging measurements were compared with final postsurgical pathologic response. A statistically significant increase, or flare, in oxyhemoglobin was observed in partial responding (n = 11) and pathologic complete responding tumors (n = 8) on day 1, whereas nonresponders (n = 5) showed no flare and a subsequent decrease in oxyhemoglobin on day 1. Oxyhemoglobin flare on day 1 was adequate to discriminate nonresponding tumors from responding tumors. Very early measures of chemotherapy response are clinically convenient and offer the potential to alter treatment strategies, resulting in improved patient outcomes.

Impact
The implementation of DOSI measurements in the clinic may be used to monitor and strategically alter treatment strategies for breast cancer patients by rapidly identifying likely nonresponders. Further advances in DOSI miniaturization and reducing barriers to access are currently under investigation in order to make this a truly portable, bedside technology. This could lead to the development of new approaches for managing patients and expediently assessing chemosensitivity for individual subjects. Because DOSI measures tumor perfusion and metabolism, it could also be used in studies of radiation and chemo-radiation therapies.

Citation
Roblyer D, Ueda S, Cerussi A, Tanamai W, Durkin A, Mehta R, Hsiang D, Butler JA, McLaren C, Chen WP, Tromberg B. Optical imaging of breast cancer oxyhemoglobin flare correlates with neoadjuvant chemotherapy response one day after starting treatment. Proc Natl Acad Sci U S A. 2011 Aug 30;108(35):14626-31. Epub 2011 Aug 18. PMC3167535

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