BackgroundSynthetic MRI (syMRI) has enabled quantification of multiple relaxation parameters (T1/T2 relaxation time [T1/T2], proton density [PD]), and their longitudinal change during neoadjuvant chemotherapy (NAC) promises to be valuable parameters for treatment response evaluation in breast cancer.PurposeTo investigate the time course changes of syMRI parameters during NAC and evaluate their value as predictors for pathological complete response (pCR) in breast cancer.Study TypeRetrospective, longitudinal.PopulationA total of 129 women (median age, 50 years; range, 28–69 years) with locally advanced breast cancer who underwent NAC; all performed multiple conventional breast MRI examinations with added syMRI during NAC.Field Strength/SequenceA 3.0 T, T1‐weighted dynamic contrast enhanced and syMRI acquired by a multiple‐dynamic, multiple‐echo sequence.AssessmentBreast MRI was set at four time‐points: baseline, after one cycle, after three or four cycles of NAC and preoperation. SyMRI parameters and tumor diameters were measured and their changes from baseline were calculated. All parameters were compared between pCR and non‐pCR. Interaction between syMRI parameters and clinicopathological features was analyzed.Statistical TestsMann–Whitney U tests, random effects model of repeated measurement, receiver operating characteristic (ROC) analysis, interaction analysis.ResultsMedian synthetic T1/T2/PD and tumor diameter generally decreased throughout NAC. Absolute T1 at early‐NAC, T1, and PD at mid‐NAC were significantly lower in the pCR group. After early‐NAC, the T1 change was significantly higher in the pCR (median ± IQR, 18.17 ± 11.33) than the non‐pCR group (median ± IQR, 10.90 ± 10.03), with the highest area under the ROC curves (AUC) of 0.769 (95% CI, 0.684–0.838). Interaction analysis showed that histological grade III patients had higher odds ratio (OR) (OR = 1.206) compared to grade II patients (OR = 1.067).Data ConclusionSynthetic T1 changes after one cycle of NAC maybe useful for early evaluating NAC response in breast cancer during whole treatment cycles. However, its discriminative ability is significantly affected by histological grade.Evidence Level4Technical EfficacyStage 2.