Abstract Background: To evaluate the utility of 68Ga-HER2 PET/CT in predicting pathological response to neoadjuvant therapy (NAT) in HER2-positive breast cancer. Methods: This prospective study included 45 newly diagnosed HER2-positive breast cancer patients requiring NAT. Patients underwent at least 4 cycles of NAT with trastuzumab plus pertuzumab or pyrrolizidine alkaloids. Post-NAT surgery was performed. Eligibility required age ≥18 years, stage II-IIIC HER2-positive breast cancer. Exclusion criteria included pregnancy or lactation, presence of severe comorbidities, inability to tolerate systemic therapy or surgery, and distant metastatic disease. 68Ga-HER2 PET/CT scans were obtained pre-NAT (PET1), at the end of cycle 2 (PET2), and pre-surgery (PET3). Standardized uptake values (SUVmax) were measured for the primary tumor and involved lymph nodes. The calculation of ΔSUVmax was performed according to the following formula: ΔSUVmax1 =(PET2 SUVmax-PET1 SUVmax)/PET1 SUVmax ×100% ΔSUVmax2 =(PET3 SUVmax-PET1 SUVmax)/PET1 SUVmax ×100% Pathological response following NAT was assessed using both the Miller PET3: 0.12±0.39 vs 1.67±2.94, P=0.014). Optimal cutoff values for predicting pCR were: primary tumor SUVmax ≤1.15 at PET2 (AUC=0.738), ≤0.50 at PET3 (AUC=0.735); absolute ΔSUVmax≥61.14% at PET2 (AUC=0.742), and ≥71.63% at PET3 (AUC=0.743). Using the PET2 SUVmax and ΔSUVmax cutoff values, patients identified as NAT-sensitive at the end of cycle 2 had an 84.62% pCR rate, which was 14.17% higher compared to the overall pCR rate without the use of this imaging modality. Conclusion: Our data indicate that 68Ga-HER2 PET/CT assessment of early 68Ga-HER2 uptake changes may predict the NAT efficacy in patients with HER2-positive breast cancer, demonstrating a potential evaluation stratergy for early and late treatment response. Keywords: HER2-positive breast cancer, 68Ga-HER2, PET/CT, neoadjuvant therapy, pCR Clinical trial registration number: ChiCTR2400092565 (Chinese Clinical Trial Registry) Representative Images: The figure below presents sequential 68Ga-HER2 PET/CT scans of a HER2-positive breast cancer patient obtained pre-NAT, at the end of cycle 2, and pre-surgery. A: Baseline scan demonstrated a soft tissue lesion measuring approximately 2.3 × 2.2 cm in the left breast, with marked radiotracer uptake and a maximum SUV of 10.1. B: At the end of the second cycle, imaging revealed a residual lesion of approximately 2.2 × 1.0 cm in the same region, without abnormal radiotracer accumulation. C: Preoperative imaging demonstrated a further reduction in lesion size to approximately 2.0 × 0.6 cm, with no abnormal tracer uptake detected. Citation Format: Y. Liu, S. Gao, X. Zhao, X. Zhang. Predicting pathological response to neoadjuvant therapy in HER2-positive breast cancer by using 68Ga-HER2 PET/CT: a prospective study abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-06-30.
Liu et al. (Tue,) studied this question.