Synapse - Detection of HER2-low lesions using HER2-targeted PET imaging in patients with metastatic breast cancer: A paired HER2 PET and tumor biopsy analysis

Detection of HER2-low lesions using HER2-targeted PET imaging in patients with metastatic breast cancer: A paired HER2 PET and tumor biopsy analysis Journal Article

Authors:	Yeh, R.; Pareja, F.; Shobeiri, P.; Ross, D.; Jayaprakasam, V. S.; Razmaria, A. A.; Drago, J. Z.; Mauguen, A.; Lyashchenko, S. K.; Zeglis, B. M.; Lewis, J. S.; Ulaner, G. A.
Article Title:	Detection of HER2-low lesions using HER2-targeted PET imaging in patients with metastatic breast cancer: A paired HER2 PET and tumor biopsy analysis
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-positive (33%) and 6 were HER2-low (67%); in the 89Zr-pertuzumab cohort, 2 were HER2-positive (29%) and 5 were HER2-low (71%). In the 89Zr-ss-pertuzumab cohort (NCT04692831), 7 patients underwent recent biopsies of 8 total lesions demonstrating 1 HER2-positive (12%), 5 HER2-low (62%), and 2 HER2-0 lesions (25%). HER2 PET SUVmax of biopsied lesions were compared between HER2-positive and HER2-low lesions for the combination of all 3 radiotracer cohorts. HER2-low lesions had a significantly higher SUVmax (median, 12.7; interquartile range, 8.05) than did HER2-positive lesions (median, 6.4; interquartile range, 1.98; P 5 0.01). Conclusion: HER2 PET imaging with 89Zr-radiolabeled antibodies detects HER2-low lesions in addition to HER2-positive lesions in patients with mBC, suggesting its ability to visualize the entire spectrum of HER2 expression. All prior false positives on 89Zr-trastuzumab and 89Zr-pertuzumab PET scans were reclassified as HER2-low. Lesion SUVmax is not reliable in differentiating HER2-positive from HER2-low lesions; however, it may be useful in distinguishing lesions expressing HER2 from HER2-0 lesions. COPYRIGHT © 2025 by the Society of Nuclear Medicine and Molecular Imaging.
Keywords:	immunohistochemistry; adult; controlled study; human tissue; aged; middle aged; retrospective studies; positron emission tomography; metabolism; metastasis; computer assisted tomography; breast cancer; epidermal growth factor receptor 2; cohort analysis; tumor biopsy; pathology; diagnostic imaging; breast neoplasms; retrospective study; biopsy; breast tumor; positron-emission tomography; neoplasm metastasis; receptor, erbb-2; radioisotope; metastatic breast cancer; pet; radioisotopes; zirconium; zirconium-89; zirconium 89; her2; pertuzumab; clinical trial (topic); erbb2 protein, human; procedures; maximum standardized uptake value; high throughput sequencing; humans; human; male; female; article; trastuzumab deruxtecan
Journal Title:	Journal of Nuclear Medicine
Volume:	66
Issue:	6
ISSN:	0161-5505
Publisher:	Society of Nuclear Medicine
Date Published:	2025-06-01
Start Page:	873
End Page:	879
Language:	English
DOI:	10.2967/jnumed.124.269227
PUBMED:	40341092
PROVIDER:	scopus
PMCID:	PMC12175990
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-105007355798&doi=10.2967%2fjnumed.124.269227&partnerID=40&md5=bf618ff5b8d2c03ea8dc4a34ced6539f
Notes:	Article -- Source: Scopus