Prospective Comparison of FDG PET, and Contrast-Enhanced MRI for Predicting Pathologic Response after Neoadjuvant Chemotherapy in Breast Cancer

Assessment of pathologic complete response (pCR) following neoadjuvant chemotherapy (NAC) remains an unmet clinical need in breast cancer. Fibroblast activation protein inhibitor (FAPI) PET targets the tumor microenvironment and may therefore enhance response evaluation after NAC. This study aimed to compare the performance of [68Ga]Ga-FAPI-04 PET, [18F]FDG PET, and contrast-enhanced MRI for predicting pathologic response after NAC in breast cancer, with separate analyses for primary breast lesions and axillary lymph nodes. MethodsIn this prospective single-center diagnostic accuracy study, 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. Quantitative PET parameters were evaluated for primary tumors and axillary lymph nodes. pCR was defined as ypT0/isN0. Significant variables identified in univariable analyses were further explored using least absolute shrinkage and selection operator (LASSO) analysis, and receiver-operating-characteristic (ROC) analysis was performed to assess diagnostic performance. Fibroblast activation protein expression was also assessed by immunohistochemistry in paired pre- and post-therapy tumor specimens from a subset of patients. ResultsTwenty-four patients completed the study protocol, yielding 25 primary lesions and 44 metastatic lymph nodes across 27 axillary compartments. Overall patient-level pCR was achieved in 13 of 24 patients (54.17%). The lesion-level pCR rate was 60.00% (15/25) for primary breast lesions, and the node-level pCR rate was 72.73% (32/44) for axillary lymph nodes. For primary tumor response, post-therapy [68Ga]Ga-FAPI-04 SUVmax showed the highest diagnostic performance (AUC, 0.84; sensitivity, 80.00%; specificity, 80.00%; accuracy, 80.00%), whereas the optimal [18F]FDG parameter was {Delta} TBR% (AUC, 0.747). For nodal response, post-therapy [68Ga]Ga-FAPI-04 SULmean showed the highest diagnostic performance (AUC, 0.89; sensitivity, 91.67%; specificity, 81.25%; accuracy, 84.09%) and was significantly different from the best [18F]FDG parameter ({Delta} SULmax%, AUC, 0.669) on DeLong testing (P < 0.05). MRI achieved AUCs of 0.733 for primary lesions and 0.770 for lymph nodes. Stromal FAP expression positively correlated with [68Ga]Ga-FAPI-04 SUVmax and was markedly reduced in lesions achieving pCR. ConclusionPost-therapy [68Ga]Ga-FAPI-04 PET may serve as a promising adjunctive imaging biomarker for predicting pathologic response after NAC in breast cancer, particularly for axillary nodal assessment. These findings suggest that FAPI PET may provide clinically relevant information for preoperative evaluation of residual disease burden, potentially contributing to more individualized surgical planning and treatment decision-making.