使用HER2靶向PET成像检测转移性乳腺癌患者的HER2低表达病变:HER2 PET与肿瘤活检配对分析
Detection of HER2-Low Lesions Using HER2-Targeted PET Imaging in Patients with Metastatic Breast Cancer: A Paired HER2 PET and Tumor Biopsy Analysis.
作者信息
Yeh Randy, Pareja Fresia, Shobeiri Parnian, Ross Dara, Jayaprakasam Vetri S, Razmaria Ali Aria, Drago Joshua Z, Mauguen Audrey, Lyashchenko Serge K, Zeglis Brian M, Lewis Jason S, Ulaner Gary A
机构信息
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York;
Department of Radiology, Weill Cornell Medical College, New York, New York.
出版信息
J Nucl Med. 2025 Jun 2;66(6):873-879. doi: 10.2967/jnumed.124.269227.
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 Zr-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. A retrospective study was conducted of mBC patients who previously enrolled in 2 prospective HER2 PET imaging trials: NCT02286843 using Zr-trastuzumab and Zr-pertuzumab and NCT04692831 using Zr-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. SUV of biopsied lesions were compared between pathologic classifications to determine whether lesion uptake intensity could differentiate between HER2-positive and HER2-low lesions. All prior false-positive lesions on HER2 PET scans from NCT02286843 were reclassified as HER2-low (instead of HER2-negative). In the Zr-trastuzumab cohort, 3 lesions were HER2-positive (33%) and 6 were HER2-low (67%); in the Zr-pertuzumab cohort, 2 were HER2-positive (29%) and 5 were HER2-low (71%). In the Zr-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 SUV 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 SUV (median, 12.7; interquartile range, 8.05) than did HER2-positive lesions (median, 6.4; interquartile range, 1.98; = 0.01). HER2 PET imaging with Zr-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 Zr-trastuzumab and Zr-pertuzumab PET scans were reclassified as HER2-low. Lesion SUV 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.
曲妥珠单抗德瓦鲁单抗(T-DXd)是一种靶向人表皮生长因子受体2(HER2)的抗体药物偶联物,在先前接受过治疗的HER2低表达转移性乳腺癌(mBC)患者中显示出显著疗效,为这一患者群体提供了一种新的治疗选择。先前使用锆标记抗体进行HER2 PET研究时,HER2阳性恶性肿瘤的成像假阳性率较高,限制了研究结果。在这项回顾性研究中,我们调查这些假阳性(病理检查为HER2阴性)是否可由HER2低表达病变解释。 对先前参加过2项前瞻性HER2 PET成像试验的mBC患者进行了回顾性研究:使用锆曲妥珠单抗和锆帕妥珠单抗的NCT02286843以及使用锆ss-帕妥珠单抗的NCT04692831。如果在2个月内进行了配对的HER2 PET扫描和活检,则纳入患者。在总共56例患者中,23例符合纳入标准。收集活检病变的病理结果,无需重复解读,并将病变分类为HER2阳性、HER2低表达或HER2阴性。比较不同病理分类的活检病变的SUV,以确定病变摄取强度是否可以区分HER2阳性和HER2低表达病变。 NCT02286843中HER2 PET扫描上所有先前的假阳性病变都重新分类为HER2低表达(而非HER2阴性)。在锆曲妥珠单抗队列中,3个病变为HER2阳性(33%),6个为HER2低表达(67%);在锆帕妥珠单抗队列中,2个为HER2阳性(29%),5个为HER2低表达(71%)。在锆ss-帕妥珠单抗队列(NCT04692831)中,7例患者对总共8个病变进行了近期活检,显示1个HER2阳性(12%),5个HER2低表达(62%),2个HER2阴性病变(25%)。比较了所有3个放射性示踪剂队列中HER2阳性和HER2低表达病变的活检病变的HER2 PET SUV。HER2低表达病变的SUV(中位数为12.7;四分位间距为8.05)显著高于HER2阳性病变(中位数为6.4;四分位间距为1.98;P = 0.01)。 使用锆标记抗体的HER2 PET成像除了能检测mBC患者的HER2阳性病变外,还能检测HER2低表达病变,表明其能够可视化HER2表达的整个范围。锆曲妥珠单抗和锆帕妥珠单抗PET扫描上所有先前的假阳性都重新分类为HER2低表达。病变SUV在区分HER2阳性和HER2低表达病变方面不可靠;然而,它可能有助于区分表达HER2的病变和HER2阴性病变。