[68Ga]Ga-HER2 Affibody PET/CT for early prediction of neoadjuvant therapy outcome in HER2-positive breast cancer

Background Neoadjuvant therapy (NAT) has become a standard treatment for HER2-positive breast cancer. However, patient responses vary substantially, and reliable methods for early response assessment are still lacking. This study aimed to evaluate the value of [ ⁶⁸ Ga]Ga-HER2 Affibody PET/CT for the early assessment of treatment outcome by predicting pathological complete response (pCR) in HER2-positive breast cancer. Results 32 of the 54 enrolled patients achieved pCR (59.3%). Following two NAT cycles, [ ⁶⁸ Ga]Ga-HER2 Affibody PET/CT parameters decreased from baseline in all patients ( P < 0.001). Early percentage changes in PET parameters (ΔSUV%, ΔSUL%, ΔTLA%, ΔTBR%) and their absolute values after the second NAT cycle were associated with pCR (r range: -0.658 to -0.273; P < 0.05). ΔTBR% demonstrated the best predictive value for pCR (AUC = 0.918), with 93.8% sensitivity and 86.4% specificity at a cutoff of -70.5%. In contrast, tumor size assessment based on RECIST 1.1 showed lower predictive performance, with a sensitivity of 56.3% (18/32) and a specificity of 45.5% (10/22). Conclusion This study demonstrates the potential of [ ⁶⁸ Ga]Ga-HER2 Affibody PET/CT to predict NAT outcome early in HER2-positive breast cancer, which could facilitate subsequent treatment optimization.