MRI is commonly used to evaluate breast cancer response to neoadjuvant chemotherapy. Image registration algorithms aid diagnostic accuracy by correcting changes in patient position across visits. A novel technique, Fast Longitudinal Image REgistration (FLIRE), was evaluated by comparison to a standard algorithm optimized for breast tissue, DRAMMS. Breast images acquired over the course of neoadjuvant treatment were registered to baseline images. FLIRE runtime was 5 minutes (~20× faster). With this fast processing time, FLIRE performed within 2.5-10.2% of optimized DRAMMS in similarity measures. Overall accuracy and computation speed for FLIRE with default arguments demonstrates promise for clinical time-sensitive applications.