Variability in diagnostic performance of breast dynamic contrast-enhanced MRI has highlighted the need for improved standardization. While guidance exists on some aspects of the technique, currently, there is no standardized method for selecting repetition time and flip angle, which are important determinants of image contrast. This study develops a theoretical framework for quantitative optimization of temporal aspects of dynamic contrast-enhanced MRI based on area under the receiver operating curve. Optimizations in simulation demonstrate the potential for increases in area under the receiver operating characteristic curve by up to 0.20 and specificity at a sensitivity of 90% by up to 19%, depending on the protocol. These results suggest that careful selection of repetition time and flip angle can improve diagnostic performance and identify these quantities as potentially important parameters for future standardization. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.