This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Optimal management of patients with locally advanced breast cancer (LABC) remains a complex therapeutic problem. LABC represents 5-20% of all newly diagnosed breast cancers in the United States with a higher incidence in medically underserved areas. Over the years, treatment for LABC has been evolving from undergoing a radical mastectomy to the use of neoadjuvant chemotherapy followed by a mastectomy or breast conservation therapy. The optimal intensity and duration of neoadjuvant chemotherapy for LABC still remains controversal due to the difficulty of evaluating response to therapy. Presently, response to treatment is measured by physical exam, mammography, and/or ultrasound. Several studies have showed significant discrepancies between the clinical assessment or response to neoadjuvant chemotherapy and the pathologic assessment of response found in post-therapy surgical specimens. Similar studies have shown that patients achieving pathologic macroscopic complete response have a better prognosis that those patients left with residual macroscopic disease at the time of surgery. Consequently, it is very important to determine the optimal timing of the local surgical treatment of LABC patients. The goal would be to prevent over and under treatment of patients with neoadjuvant chemotherapy. Many imaging modalities are investigating this specific problem such as positron emission tomography (PET) and contrast enhanced magnetic resonance imaging (MRI) but these modalities are expensive, complex, and have limited access to the general public. Preliminary results with a non-invasive technique, Photon Migration Spectroscopy (PMS), on normal volunteers and patients receiving chemotherapy have shown excellent sensitivity to breast tissue functional changes. These changes were correlated with a decrease in overall tumor dimensions in the cases of LABC subjects. Photon Migration Spectroscopy is a non-invasive optical technique that utilizes intensity-modulated, near-infrared (NIR) light to quantitatively measure optical properties in thick tissues. Optical properties (absorption, us and scattering us' parameters) derived from PMS measurements can be used to construct low-resolution (0.5-1 cm) functional images of tissue hemoglobin (total, oxy, and deoxy forms), oxygen saturation, blood volume fraction, water content, fat content, and cellular structure. Unlike conventional NIR transillumination, PMS enables quantitative analysis of tissue absorption and scattering parameters in a single non-invasive measurement. The unique functional information provided by PMS makes it well suited to characterizing tumors in thick tissues. Measurements are performed using a non-invasive, multi-wavelength, diode-laser PMS device. Some preliminary results show that the metabolic changes are detectable in locally advanced breast cancer tumors undergoing treatment with neoadjuvant chemotherapy using photon migration techniques. The measurements provide quantitative optical property values that reflect changes in tissue perfusion, oxygen consumption, and cell/matrix development. Our pilot study will be to perform sequential Photon Migration Spectroscopy (PMS) on tumors of breast cancer patients undergoing neoadjuvant chemotherapy. PMS readings will be obtained prior to and subsequent to each chemotherapy cycle. Concurrent, baseline physical exams, routine labs, pulse oximetry, and ultrasound measurements of the breast tumor will also be collected. Immunohistopathology will be performed on both the pre-neoadjuvant chemotherapy and the post-surgical tumor samples which are obtained in the routine standard of care for patients undergoing neoadjuvant chemotherapy. All this data will be then analyzed with statistical models to see whether PMS can determine accurately and quantify the physiological parameters of breast cancer tumors undergoing chemotherapy and the amount of residual disease still present in the surgical specimen.
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