[68Ga]Ga-labeled fibroblast activation protein inhibitor PET/CT for monitoring neoadjuvant chemotherapy responses in breast cancer subtypes

[68Ga]Ga-labeled fibroblast activation protein inhibitor ([68Ga]Ga-FAPI) PET/CT has shown promising potential in predicting pathological complete response (pCR) in patients with breast cancer (BC). However, current literature lacks comprehensive data addressing molecular subtype-specific variations. This study aims to evaluate the predictive value of [68Ga]Ga-FAPI-04 PET/CT across different BC molecular subtypes. This preliminary study enrolled 66 patients with clinical stage II-III BC scheduled for neoadjuvant chemotherapy (NAC). Patients underwent [68Ga]Ga-FAPI-04 PET/CT at baseline (PET1), after two NAC cycles (PET2), and presurgery (PET3). The maximum standardized uptake value (SUVmax) and its percentage change from baseline (ΔSUVmax) were calculated for the primary tumors. Pathological response was assessed postsurgery. Patients were stratified into three molecular subtypes: hormone receptor-positive/HER2-negative (HR+/HER2−), HER2-positive (HER2+), and triple-negative breast cancer (TNBC). Receiver operating characteristic (ROC) curve analysis was utilized to evaluate the predictive performance of FAPI parameters for pCR. Among the 66 patients, 21 (31.8%) achieved pCR, with rates varying significantly across molecular subtypes (P = 0.002). Baseline [68Ga]Ga-FAPI-04 uptake (SUVmax1) was significantly higher in HER2+ tumors (17.98 ± 6.34) compared to HR+/HER2− (14.37 ± 4.11) and TNBC tumors (15.00 ± 5.25) (P = 0.043). The predictive value of [68Ga]Ga-FAPI-04 parameters for pCR was highly dependent on molecular subtype. In HER2+ tumors, early response assessment was most effective, with ΔSUVmax1 (change after two cycles) being the strongest predictor (area under the curve [AUC] = 0.799). A cutoff of − 69.49% yielded 85.7% sensitivity and 72.7% specificity. For TNBC, late-phase parameters demonstrated exceptional accuracy, with SUVmax3 (presurgery) achieving near-perfect discrimination (AUC = 0.967). A cutoff of ≤ 2.19 provided 100% sensitivity and 95.5% specificity. In HR+/HER2− tumors, late-phase parameters were most predictive, with SUVmax3 showing excellent performance (AUC = 0.948). A cutoff of ≤ 1.58 yielded 75.0% sensitivity and 91.7% specificity. The predictive efficacy of [68Ga]Ga-FAPI-04 PET/CT for pCR demonstrates substantial variability across BC molecular subtypes. These findings underscore the potential of [68Ga]Ga-FAPI-04 PET/CT to inform subtype-specific, personalized treatment approaches.