Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA.
Edward Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, USA.
Breast Cancer Res Treat. 2018 Jun;169(3):523-530. doi: 10.1007/s10549-018-4696-z. Epub 2018 Feb 13.
To evaluate whether tumor uptake of [Zr]trastuzumab can distinguish HER2-positive from HER2-negative breast cancer.
Women with HER2-positive (n = 34) and HER2-negative (n = 16) breast cancer underwent PET/CT 5 ± 2 days following [Zr]trastuzumab administration. HER2 status was determined based on immunohistochemistry and/or fluorescence in situ hybridization of primary or metastatic/recurrent tumor. Tumor [Zr]trastuzumab uptake was assessed qualitatively and semiquantitatively as maximum standardized uptake value (SUV), and correlated with HER2 status. Additionally, intrapatient heterogeneity of [Zr]trastuzumab uptake was evaluated.
On a per-patient basis, [Zr]trastuzumab-PET/CT was positive in 30/34 (88.2%) HER2-positive and negative in 15/16 (93.7%) HER2-negative patients. Considering all lesions, the SUV was not significantly different in patients with HER2-positive versus HER2-negative disease (p = 0.06). The same was true of when only hepatic lesions were evaluated (p = 0.42). However, after excluding hepatic lesions, tumor SUV was significantly higher in HER2-positive compared to HER2-negative patients (p = 0.003). A cutoff SUV of 3.2, determined by ROC analysis, demonstrated positive-predictive value of 83.3% (95% CI 65.3%, 94.4%), sensitivity of 75.8% (57.7%, 88.9%), negative-predictive value of 50% (24.7%, 75.3%), and specificity of 61.5% (95% 31.6%, 86.1%) for differentiating HER2-positive from HER2-negative lesions. There was intrapatient heterogeneity of [Zr]trastuzumab uptake in 20% of patients with multiple lesions.
[Zr]trastuzumab has the potential to characterize the HER2 status of the complete tumor burden in patients with breast cancer, thus obviating repeat or multiple tissue sampling to assess intrapatient heterogeneity of HER2 status.
评估[Zr]曲妥珠单抗摄取能否区分 HER2 阳性与 HER2 阴性乳腺癌。
HER2 阳性（n=34）和 HER2 阴性（n=16）乳腺癌患者在[Zr]曲妥珠单抗给药后 5±2 天行 PET/CT。HER2 状态基于原发性或转移性/复发性肿瘤的免疫组织化学和/或荧光原位杂交来确定。通过最大标准化摄取值（SUV）定性和半定量评估肿瘤[Zr]曲妥珠单抗摄取，并与 HER2 状态相关联。此外，还评估了[Zr]曲妥珠单抗摄取的患者内异质性。
在每位患者的基础上，[Zr]曲妥珠单抗-PET/CT 在 30/34（88.2%）HER2 阳性患者中呈阳性，在 15/16（93.7%）HER2 阴性患者中呈阴性。考虑到所有病变，HER2 阳性与 HER2 阴性疾病患者的 SUV 无显著差异（p=0.06）。当仅评估肝病变时也是如此（p=0.42）。然而，在排除肝病变后，HER2 阳性患者的肿瘤 SUV 显著高于 HER2 阴性患者（p=0.003）。通过 ROC 分析确定的 SUV 截断值 3.2 显示出区分 HER2 阳性与 HER2 阴性病变的阳性预测值为 83.3%（95%CI 65.3%，94.4%）、灵敏度为 75.8%（57.7%，88.9%）、阴性预测值为 50%（24.7%，75.3%）和特异性为 61.5%（95%CI 31.6%，86.1%）。在 20%具有多个病变的患者中存在[Zr]曲妥珠单抗摄取的患者内异质性。
[Zr]曲妥珠单抗有可能描述乳腺癌患者完整肿瘤负荷的 HER2 状态，从而避免重复或多次组织取样以评估 HER2 状态的患者内异质性。
