Diagnostic Performance of 68Ga-FAPI PET/CT Versus 18F-FDG PET/CT in Evaluating Neoadjuvant Therapy Pathological Response in Breast Cancer

Abstract Accurate pathological response assessment of breast cancer following neoadjuvant therapy (NAT) is clinically critical but lacks robust imaging methods, so this study evaluated the diagnostic accuracy of 18 F-fluorodeoxyglucose (FDG) PET/CT and 68 Ga-fibroblast activation protein inhibitor (FAPI) PET/CT in clinically node positive (cN+) breast cancer patients receiving NAT. This prospective study enrolled pathologically confirmed breast cancer patients who underwent NAT and both PET/CT scans preoperatively. The maximum standardized uptake value (SUVmax) was measured and an optimal 68 Ga-FAPI PET/CT threshold was determined via receiver operating characteristic (ROC) curve analysis. Among 75 patients, 33 (44.0%) achieved pathological complete response (pCR). SUVmax was significantly lower in the ypT0/Tis group compared to the ypT+ group for both 18 F-FDG PET/CT (1.45 ± 0.55 vs. 5.19 ± 4.69, p < 0.001) and 68 Ga-FAPI PET/CT (1.59 ± 1.22 vs. 10.45 ± 8.54, p < 0.001). In the overall cohort, 68 Ga-FAPI PET/CT demonstrated higher sensitivity in detecting residual disease compared to 18 F-FDG PET/CT (0.8 vs. 0.6, p = 0.003), with comparable specificity (0.9 vs. 0.9, p = 1.00). Exploratory subgroup analysis found that 68 Ga-FAPI PET/CT had superior sensitivity compared to 18 F-FDG PET/CT in the hormone receptor-positive (HR + ) group (0.8 vs. 0.6, p = 0.02). These findings show that 68 Ga-FAPI PET/CT outperforms 18 F-FDG PET/CT in identifying residual breast lesions after NAT in cN+ patients, particularly among HR+ patients, which would guide further treatment strategies after NAT.