⁶⁸Ga-HER2 PET/CT for Predicting Pathologic Response to Neoadjuvant Therapy at Early Treatment and Preoperative Stages...

This study aimed to evaluate the predictive performance of ⁶⁸Ga-HER2 PET/CT in assessing pathologic response to neoadjuvant therapy (NAT) in human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Methods: In total, 45 patients with newly diagnosed HER2-positive breast cancer eligible for NAT were enrolled. All participants received at least 4 cycles of trastuzumab combined with pertuzumab or pyrotinib-based therapy, followed by surgery. ⁶⁸Ga-HER2 PET/CT was performed at baseline (PET1), at the end of the second therapy cycle (PET2), and before surgery (PET3). The SUV_max of primary breast tumors and metastatic lymph nodes were recorded. Results: Pathologic complete response (pCR) was achieved in 31 patients (70%), whereas 13 (30%) showed non-pCR. The SUV_max at PET1 did not differ significantly between pCR and non-pCR groups (3.76 ± 1.97 vs. 3.79 ± 2.71, P = 0.349). However, the SUV_max at PET2 and PET3 were significantly lower in the pCR group compared with the non-pCR group (PET 2: 0.45 ± 0.71 vs. 2.01 ± 2.36, P = 0.008; PET3: 0.12 ± 0.39 vs. 1.67 ± 2.94, P = 0.014). The optimal cutoff values for predicting pCR included an SUV_max of no more than 1.15 (area under the curve [AUC] = 0.738) at PET2 and no more than 0.50 (AUC = 0.735) at PET3 and a ΔSUV_max of at least 61% (AUC = 0.742) at PET2 and at least 72% (AUC = 0.743) at PET3. Application of the PET2 cutoff thresholds for SUV_max and ΔSUV_max identified a therapy-sensitive subgroup, which had a positive predictive value for pCR of 85%-representing a 15% higher absolute likelihood of pCR compared with the nonsensitive subgroup-while the method provided a negative predictive value of approximately 60%. Conclusion: Dynamic changes in ⁶⁸Ga-HER2 PET/CT uptake during NAT provide an effective early indicator of therapeutic sensitivity in HER2-positive breast cancer, supporting its value for predicting pathologic response at both early treatment and preoperative stages.