Detection of HER2-Low Lesions Using HER2-Targeted PET Imaging in Patients with Metastatic Breast Cancer: A Paired HER2 PET and Tumor Biopsy Analysis

作者：Randy Yeh, Fresia Pareja, P. Shobeiri, Dara Ross, V. S. Jayaprakasam, A. Razmaria, J. Drago, A. Mauguen, S. Lyashchenko, Brian M. Zeglis, Jason S Lewis, Gary A. Ulaner · 发表于：Journal of Nuclear Medicine · 年份：2025 · DOI：10.2967/jnumed.124.269227 · 被引用次数：8 · 研究领域：Medicine

Visual Abstract Trastuzumab deruxtecan (T-DXd), a human epidermal growth factor receptor 2 (HER2)–targeted antibody–drug conjugate, demonstrated remarkable efficacy in previously treated patients with HER2-low metastatic breast cancer (mBC), marking a new therapeutic option for this patient population. Prior studies with HER2 PET using 89Zr-radiolabeled antibodies were limited by high rates of imaging false positives for HER2-positive malignancy. In this retrospective study, we investigate whether these false positives (HER2-negative on pathology) could be explained by HER2-low lesions. Methods: A retrospective study was conducted of mBC patients who previously enrolled in 2 prospective HER2 PET imaging trials: NCT02286843 using 89Zr-trastuzumab and 89Zr-pertuzumab and NCT04692831 using 89Zr-ss-pertuzumab. Patients were included if paired HER2 PET scan and biopsy were performed within a 2-mo period. Of 56 total patients, 23 patients met the inclusion criteria. Pathology results for biopsied lesions were collected, without repeat interpretation, and lesions were classified as HER2-positive, HER2-low, or HER2-0. SUVmax of biopsied lesions were compared between pathologic classifications to determine whether lesion uptake intensity could differentiate between HER2-positive and HER2-low lesions. Results: All prior false-positive lesions on HER2 PET scans from NCT02286843 were reclassified as HER2-low (instead of HER2-negative). In the 89Zr-trastuzumab cohort, 3 lesions were HER2-...