The goal of this project is the improved integration of MRI-based quantitative imaging (Ql) for evaluating response to treatment in clinical trials of women receiving pre-operative (neoadjuvant) treatment for breast cancer. We will build on the existing ISPY clinical trials program, which encompasses a series of breast cancer trials focused in the neoadjuvant setting. ISPY-1 started in 2002 with correlative studies of imaging and tissue biomarkers in association with standard of care chemotherapy and has evolved toward individualized treatment with targeted therapies. ISPY-2, which opened in March 2010, follows an adaptive phase II design to evaluate multiple targeted therapies for breast cancer. Randomization to the multiple treatment arms adapts based in part on the MRI measurement of tumor volume as a result of preliminary findings from ACRIN 6657, the imaging component of ISPY-1. The proposed Quantitative Imaging Network (QIN) project will focus in three areas critical to maximizing the effectiveness and reliability of Ql for evaluating drug treatment strategies for breast cancer. Under the first aim, we will develop a quality assurance (QA) process that will be used to implement more objective criteria for initial site qualification, ongoing assessment of image quality and exam acceptance for quantitative analysis. Under the second aim, we will conduct a repeatability study in a patient cohort similar to ISPY-2 to obtain important information about the variability of quantitative measurements made from breast MRI that can be used to improve the interpretation of response results. Under the third aim, we will test several new imaging metrics for predicting treatment response in both ISPY and a phase II trial of neoadjuvant letrozole for treatment of post- menopausal ER+ DCIS. This project will be conducted in partnership with the American College of Radiology Imaging Network (ACRIN) Imaging Core and industrial partner Sentinelle Medical, Inc. In order to maximize the efficiency with which products of this QIN project can be translated into clinical practice, both the ACRIN TRIAD informatics system and the Sentinelle Aegis software system will communicate with the ISPY-2 TRANSCEND informatics system linking imaging with the caBIG supported ISPY-2 trial database.