Simple SummaryIn breast cancer (BC) patients, neoadjuvant chemotherapy (NAC) is chemotherapy given before surgery. Complete pathological response (pCR) to NAC is defined as the absence of residual tumor cells on microscopy both in the breast and in the axillary or distant lymph nodes in the surgical specimen. Achievement of pCR is associated with longer disease-free survival (DFS), namely survival without tumor recurrence. [18F]Fluorodeoxyglucose (18F-FDG) positron emission tomography may represent a complementary imaging tool in predicting pCR to NAC. We found (PET)-derived parameters predicting DFS in patients with BC with different molecular subtypes (based on the presence of specific receptors in the tumor). Furthermore, we demonstrated that some of these parameters predicting DFS are significantly different in patients achieving pCR compared to those without pCR after NAC. Larger study samples are needed to confirm these preliminary findings.AbstractWe investigated whether baseline [18F] Fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)-derived semiquantitative parameters could predict disease-free survival (DFS) in patients with grade III breast cancer (BC) of different molecular subtypes candidate to neoadjuvant chemotherapy (NAC). For each18F-FDG-PET/CT scan, the following parameters were calculated in the primary tumor (SUVmax, SUVmean, MTV, TLG) and whole-body (WB_SUVmax, WB_MTV, and WB_TLG). Receiver operating characteristic (ROC) analysis was used to determine the capability to predict DFS and find the optimal threshold for each parameter. Ninety-five grade III breast cancer patients with different molecular types were retrieved from the databases of the University Hospital of Padua and the University Hospital of Ferrara (luminal A: 5; luminal B: 34; luminal B-HER2: 22; HER2-enriched: 7; triple-negative: 27). In luminal B patients, WB_MTV (AUC: 0.75; best cut-off: WB_MTV > 195.33; SS: 55.56%, SP: 100%;p= 0.002) and WB_TLG (AUC: 0.73; best cut-off: WB_TLG > 1066.21; SS: 55.56%, SP: 100%;p= 0.05) were the best predictors of DFS. In luminal B-HER2 patients, WB_SUVmax was the only predictor of DFS (AUC: 0.857; best cut-off: WB_SUVmax > 13.12; SS: 100%; SP: 71.43%;p< 0.001). No parameter significantly affected the prediction of DFS in patients with grade III triple-negative BC. Volume-based parameters, extracted from baseline18F-FDG PET, seem promising in predicting recurrence in patients with grade III luminal B and luminal B- HER2 breast cancer undergoing NAC.