Magnetic Resonance Imaging (MRI) of the breast is a sensitive and non-invasive method for assessing both tumor morphology and physiology. In comparison to mammography and ultrasound, MRI has particular advantages for demonstrating the anatomic extent of disease and it is effective for assessing the response of primary breast tumors to pre-operative (neoadjuvant) treatment. Dynamic contrast-enhanced (DCE)-MRI and diffusion-weighted MRI (DWI) are two approaches that provide quantitative in vivo information about the state of disease and have been used to measure breast tumor changes associated with treatment. These techniques add functional information about breast cancer by sensitizing the MRI signal to tumor vascularity, known to be associated with tumor grade and aggressiveness, and water diffusion, a property affected by cell density that can reflect tumor growth as well as cell death from cytotoxic treatment, respectively. MR spectroscopic imaging (MRSI) has also been applied in the breast to study tumor metabolism, although the low spatial resolution currently limits the utility of this technique. This talk will discuss the emerging applications of functional MRI techniques for assessing breast tumor response to treatment in the neoadjuvant setting. The various roles for use of quantitative imaging in assessing neoadjuvant treatment will be considered. Imaging criteria can be the basis for patient inclusion or continuation on therapy, and can also be used as a biomarker to quantify response. Depending on how well the efficacy of an imaging biomarker has been established, it can also serve as the endpoint for evaluating the benefit of treatment, or as a surrogate endpoint for other clinically meaningful outcomes. A promising but more speculative role for imaging biomarkers is for prediction of therapeutic response. Current findings will be presented from the I-SPY (ACRIN 6657/CALGB 150007) trial, a multi-center study integrating biomarkers and imaging to maximize effectiveness of neoadjuvant treatment for patients with locally-advanced breast cancer. The experience implementing standardized MRI protocols in the multi-center setting will be discussed. This talk is intended for imaging scientists and clinical researchers involved in the diagnosis and treatment of breast cancer. It is expected that the audience will gain knowledge leading to the appropriate application of breast MRI techniques in the neoadjuvant treatment setting. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr ES08-3.