Understanding which patients with human epidermal growth factor receptor 2 (HER2)–negative or –low metastatic breast cancer (MBC) benefit from HER2-targeted strategies is urgently needed. We assessed the whole-body heterogeneity of HER2 expression on ⁸⁹Zr-trastuzumab PET (HER2 PET) and the diagnostic performance of HER2 PET in a large series of patients, including HER2-negative and -low MBC. Methods: In the IMPACT-MBC study, patients with newly diagnosed and nonrapidly progressive MBC of all subtypes were included. Metastasis HER2 status was determined by immunohistochemistry and in situ hybridization.⁸⁹Zr-trastuzumab uptake was quantified as SUV_max and SUV_mean. HER2 immunohistochemistry was related to the quantitative ⁸⁹Zr-trastuzumab uptake of all metastases and corresponding biopsied metastasis, uptake heterogeneity, and qualitative scan evaluation. A prediction algorithm for HER2 immunohistochemistry positivity based on uptake was developed. Results: In 200 patients, ⁸⁹Zr-trastuzumab uptake was quantified in 5,163 metastases, including 186 biopsied metastases. With increasing HER2 immunohistochemistry status, uptake was higher (geometric mean SUV_max of 7.0, 7.6, 7.3, and 17.4 for a HER2 immunohistochemistry score of 0, 1, 2, or 3+, respectively; P < 0.001). High uptake exceeding 14.6 (90th percentile) was observed in one third of patients with a HER2-negative or -low metastasis biopsy. The algorithm performed best when lesion site and size were incorporated (area under the curve, 0.86; 95% CI, 0.79–0.93). Conclusion: HER2 PET had good diagnostic performance in MBC, showing considerable whole-body HER2 heterogeneity and uptake above background in HER2-negative and -low MBC. This provides novel insights into HER2-negative and -low MBC compared with standard HER2 immunohistochemistry on a single biopsy.

迫切需要了解哪些人表皮生长因子受体 2 （HER2） 阴性或低转移性乳腺癌 （MBC） 患者受益于 HER2 靶向策略。我们评估了 ⁸⁹例 Zr-曲妥珠单抗 PET （HER2 PET） 上 HER2 表达的全身异质性以及 HER2 PET 在大型系列患者中的诊断性能，包括 HER2 阴性和低 MBC。方法：在 IMPACT-MBC 研究中，包括所有亚型的新诊断和非快速进展的 MBC 患者。通过免疫组化和原位杂交确定转移 HER2 状态。⁸⁹ 元Zr-曲妥珠单抗摄取被量化为 SUV_max 和 SUV_mean。HER2 免疫组化与所有转移灶的定量 ⁸⁹Zr-曲妥珠单抗摄取和相应的活检转移、摄取异质性和定性扫描评估有关。开发了一种基于摄取的 HER2 免疫组化阳性预测算法。结果：在 200 例患者中，在 5,163 例转移中定量了 ⁸⁹例 Zr-曲妥珠单抗摄取，包括 186 例活检转移。随着 HER2 免疫组化状态的增加，摄取率更高（HER2 免疫组化评分为 0、1、2 或 3+ 的几何平均 SUV_最大值分别为 7.0、7.6、7.3 和 17.4;P < 0.001）。在 1/3 的 HER2 阴性或低转移活检患者中观察到超过 14.6 （第 90 个百分位数） 的高摄取。当结合病变部位和大小时，该算法表现最佳 （曲线下面积，0.86;95% CI，0.79-0.93）。 结论：HER2 PET 在 MBC 中具有良好的诊断性能，在 HER2 阴性和低 MBC 中显示出相当大的全身 HER2 异质性和高于背景的摄取。与单次活检中的标准 HER2 免疫组化相比，这为 HER2 阴性和低 MBC 提供了新的见解。