Breast cancer is characterized by marked variability in human epidermal growth factor receptor 2 (HER2) expression across and within tumors. In routine clinical practice, obtaining repeat tissue samples from recurrent or metastatic sites is often invasive, technically difficult, and sometimes infeasible. Therefore, alternative strategies capable of reliably characterizing HER2 status and tracking treatment efficacy are needed. This study investigated the clinical utility of HER2-targeted PET/CT imaging for noninvasive evaluation of HER2 expression and longitudinal assessment of therapeutic response in breast cancer. In this exploratory investigation, data were derived from a prospective clinical study involving adult breast cancer patients who underwent both 18F-Al-NOTA-HER2-BCH PET/CT and 18F-FDG PET/CT at Beijing Cancer Hospital between June 2020 and July 2023 (ClinicalTrials.gov identifier: NCT04547309).
A total of 59 patients with a median age of 55 years were included in the analysis. Among lesions classified as HER2 immunohistochemistry (IHC) 3+, uptake on HER2-targeted PET/CT was significantly higher prior to anti-HER2 therapy compared with post-treatment imaging (median SUVmax 19.9 [95% CI: 15.7–25.3] vs 9.8 [95% CI: 5.6–14.7]; P = .006). Pretreatment SUVmax values demonstrated a statistically significant positive association with HER2 IHC status (P = .034), with substantially greater tracer accumulation observed in HER2-positive lesions than in HER2-negative lesions (17.9 ± 13.2 vs 1.1 ± 0.3; P = .007). Imaging further revealed pronounced heterogeneity in HER2 expression, both between primary tumors and metastatic deposits (22.9%) and across distinct metastatic sites (26.7%). Notably, higher baseline SUVmax values were associated with improved therapeutic response. The HER2-targeted PET/CT protocol was safely completed by all participants without adverse events. HER2-targeted PET/CT represents a feasible, safe, and quantitative imaging modality for evaluating HER2 expression in breast cancer. By enabling whole-body, noninvasive assessment of receptor status and treatment response, this approach may support more precise and individualized therapeutic decision-making in clinical oncology.
