From the Departments of *Radiology and ‡Medicine, Memorial Sloan Kettering Cancer Center; Departments of †Radiology and §Medicine, Weill Cornell Medical College; and ∥Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY.
Clin Nucl Med. 2017 Dec;42(12):912-917. doi: 10.1097/RLU.0000000000001820.
The aim of this study was to determine if imaging with Zr-trastuzumab, a human epidermal growth factor receptor 2 (HER2)-targeting PET tracer, can detect HER2-positive metastases in patients with HER2-negative primary breast cancer.
As part of an institutional review board-approved, prospective clinical trial of Zr-trastuzumab PET/CT (ClinicalTrials.gov identifier NCT02286843), a second group of 11 patients with HER2-negative primary breast cancer and known metastatic disease were recruited. Patients with confirmed HER2-negative primary breast cancer underwent Zr-trastuzumab PET/CT to screen for Zr-trastuzumab-avid lesions suggestive of unsuspected HER2-positive metastases. Zr-trastuzumab-avid lesions on PET/CT were biopsied and pathologically examined to determine HER2 status.
All 11 patients had confirmed HER2-negative primary breast cancer. Four patients demonstrated suspicious foci on Zr-trastuzumab PET/CT. Of these 4 patients, 1 patient had biopsy-proven HER2-positive metastases. The other 3 patients with suspicious Zr-trastuzumab-avid foci had biopsy demonstrating a metastasis that was HER2-negative and were considered false-positive Zr-trastuzumab PET foci. Combined with a published report of the first 9 patients, there have been a total of 20 HER2-negative primary breast cancer patients, with 3 patients (15%) having pathologically confirmed HER2-positive distant metastases and 6 (30%) with suspicious Zr-trastuzumab-avid foci that were HER2-negative on pathology, which were thus considered false-positive Zr-trastuzumab findings.
This second group of patients confirms the proof of concept that Zr-trastuzumab PET/CT detects unsuspected HER2-positive metastases in a subset of patients with HER2-negtive primary breast cancer. False-positive Zr-trastuzumab-avid foci present a challenge to using this tracer.
本研究旨在确定 Zr-曲妥珠单抗（一种人表皮生长因子受体 2（HER2）靶向 PET 示踪剂）成像是否可检测 HER2 阴性原发性乳腺癌患者的 HER2 阳性转移灶。
作为 Zr-曲妥珠单抗 PET/CT（ClinicalTrials.gov 标识符 NCT02286843）机构审查委员会批准的前瞻性临床试验的一部分，招募了第二组 11 名 HER2 阴性原发性乳腺癌且已知患有转移性疾病的患者。HER2 阴性原发性乳腺癌确诊的患者接受 Zr-曲妥珠单抗 PET/CT 检查，以筛查 Zr-曲妥珠单抗亲和性病变，提示存在未被怀疑的 HER2 阳性转移灶。对 PET/CT 上的 Zr-曲妥珠单抗亲和性病变进行活检和病理检查以确定 HER2 状态。
所有 11 名患者均经确诊患有 HER2 阴性原发性乳腺癌。4 名患者的 Zr-曲妥珠单抗 PET/CT 上显示可疑病灶。这 4 名患者中，1 名患者的活检证实存在 HER2 阳性转移灶。其余 3 名可疑 Zr-曲妥珠单抗亲和性病灶的患者活检显示 HER2 阴性转移灶，被认为是 Zr-曲妥珠单抗 PET 假阳性病灶。结合首次 9 名患者的一份已发表报告，共有 20 名 HER2 阴性原发性乳腺癌患者，其中 3 名（15%）患者的病理证实存在 HER2 阳性远处转移灶，6 名（30%）患者的可疑 Zr-曲妥珠单抗亲和性病灶的 HER2 阴性，因此被认为是 Zr-曲妥珠单抗假阳性发现。
这第二组患者证实了概念验证，即 Zr-曲妥珠单抗 PET/CT 可在一部分 HER2 阴性原发性乳腺癌患者中检测到未被怀疑的 HER2 阳性转移灶。假阳性的 Zr-曲妥珠单抗亲和性病灶给该示踪剂的应用带来了挑战。
