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A relatively new pathologic grading system, called residual cancer burden (RCB) criteria (0 to III), for assessing the response to neoadjuvant chemotherapy (NCT) of breast cancer has been reported to be more accurate than conventional pathologic criteria. This study assesses the value of 18F-FDG PET/CT in early prediction of chemotherapeutic response determined based on these criteria.Thirty-six patients with locally advanced breast cancer underwent 18F-FDG PET/CT before and after the first (just before the second) cycle of NCT. Percentage changes (%△) in SUVmax, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) between 18F-FDG PET/CT before and after the first cycle of NCT were correlated with RCB index on pathologic specimens after the completion of NCT.The %△SUVmax, %△MTV, and %△TLG in the RCB 0/I group (n = 5) were all significantly larger than those in the RCB II/III group (n = 31) (82.9%, 100%, and 100% vs 45.8%, 83.2%, and 88.0%, respectively, P < 0.01). The sensitivity/specificity/accuracy of the optimal cutoff %△SUVmax, %△MTV, and %△TLG for discriminating RCB 0/I group from RCB II/III group based on the receiver operating characteristic analysis were 80.0%/96.8%/94.4%, 100%/80.6%/83.3%, and 100%/80.6%/83.3%, respectively. The area under the curve for the 3 parameters was 0.923, 0.903, and 0.884, respectively, and not statistically different.The %Δmetabolic parameters derived from 18F-FDG PET/CT studies performed before and after the first cycle of NCT in patients with locally advanced breast cancer appear to be useful in early prediction of eventual therapy response determined based on the RCB pathologic grading system.