This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Main Objective: DOSI will be used to evaluate the patient's response to chemotherapy. The primary aim of this clinical trial is to determine whether the baseline to mid-therapy changes in the DOSI measurement of the quantitative tumor tissue optical index (TOI) can predict final complete pathologic response in breast cancer patients undergoing pre-surgical neoadjuvant chemotherapy. The secondary aims investigate the correlation between additional DOSI quantitative measurements of tumor biochemical composition obtained at other timepoints, the full range of pathologic response (i.e. complete, partial, and non-response) and any corresponding imaging measurements. DOSI and standard of care imaging (e.g. serial mammograms, serial ultrasounds, etc) and/or all MRI (e.g., SOC imaging or MRI imaging from co-enrollment in ACRIN 6657 or other studies) will be collected. ACRIN #6691 is the first optical imaging trial sponsored by ACRIN.