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

Accurate assessment of pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) remains challenging in breast cancer. This prospective single-center study compared [⁶⁸Ga]Ga-FAPI-04 PET/MRI, [¹⁸F]FDG PET/CT, and contrast-enhanced MRI for predicting pathologic response after NAC. Women with biopsy-confirmed stage II-III breast cancer underwent baseline and post-therapy [⁶⁸Ga]Ga-FAPI-04 PET/MRI, [¹⁸F]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. 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 [⁶⁸Ga]Ga-FAPI-04 SUVmax showed the highest performance (AUC, 0.84; sensitivity, specificity, and accuracy, 80.00% each); the best [¹⁸F]FDG parameter was ΔTBR% (AUC, 0.747). For nodal response, post-therapy [⁶⁸Ga]Ga-FAPI-04 SULmean showed the highest performance (AUC, 0.89; sensitivity, 91.67%; specificity, 81.25%; accuracy, 84.09%) and exceeded the best [¹⁸F]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 [⁶⁸Ga]Ga-FAPI-04 SUVmax. Post-therapy [⁶⁸Ga]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. ClinicalTrials.gov, NCT07553741, retrospectively registered.