Prospective comparison of [68Ga]Ga-FAPI-04 PET/MRI, [18F]FDG PET/CT, and contrast-enhanced MRI for predicting pathologic complete response after neoadjuvant chemotherapy in breast cancer

Abstract Purpose Accurate assessment of pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) remains challenging in breast cancer. This prospective single-center study compared [ 68 Ga]Ga-FAPI-04 PET/MRI, [ 18 F]FDG PET/CT, and contrast-enhanced MRI for predicting pathologic response after NAC. Methods Women with biopsy-confirmed stage II–III breast cancer underwent baseline and post-therapy [ 68 Ga]Ga-FAPI-04 PET/MRI, [ 18 F]FDG PET/CT, and contrast-enhanced MRI before surgery. PET parameters were analyzed for primary tumors and axillary nodes. Selected variables were evaluated using LASSO and receiver-operating-characteristic analyses. Stromal FAP expression was assessed immunohistochemically in paired specimens. Results Twenty-four patients completed the protocol, yielding 25 primary lesions and 44 metastatic lymph nodes across 27 axillary compartments. The pCR rate was 60.00% for primary lesions and 72.73% for axillary nodes. For primary-lesion response, post-therapy [ 68 Ga]Ga-FAPI-04 SUVmax showed the highest performance (AUC, 0.84; sensitivity, specificity, and accuracy, 80.00% each); the best [ 18 F]FDG parameter was ΔTBR% (AUC, 0.747). For nodal response, post-therapy [ 68 Ga]Ga-FAPI-04 SULmean showed the highest performance (AUC, 0.89; sensitivity, 91.67%; specificity, 81.25%; accuracy, 84.09%) and exceeded the best [ 18 F]FDG parameter on DeLong testing. MRI AUCs were 0.733 and 0.770 for primary and nodal disease, respectively. Stromal FAP expression correlated positively with [ 68 Ga]Ga-FAPI-04 SUVmax. Conclusion Post-therapy [ 68 Ga]Ga-FAPI-04 PET may provide useful adjunctive information for response assessment after NAC in breast cancer, particularly for axillary nodal evaluation, potentially supporting more individualized preoperative planning. Trial registration ClinicalTrials.gov, NCT07553741, retrospectively registered.