Whole-Body HER2 Heterogeneity Identified on HER2 PET in HER2-Negative, -Low, and -Positive Metastatic Breast Cancer
Bertha Eisses, Jasper van Geel, Adrienne H. Brouwers, Frederike Bensch, Sjoerd G. Elias, Evelien Kuip, Agnes Jager, Bert van der Vegt, Marjolijn N. Lub–de Hooge, Jasper Emmering, Anne I.J. Arens, Gerben J.C. Zwezerijnen, Daniëlle J. Vugts, C. Willemien Menke‐van der Houven van Oordt, Elisabeth G.E. de Vries, Carolina P. Schröder
Abstract
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 <sup>89</sup>Zr-trastuzumab PET (HER2 PET) and the diagnostic performance of HER2 PET in a large series of patients, including HER2-negative and -low MBC. <b>Methods:</b> 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.<sup>89</sup>Zr-trastuzumab uptake was quantified as SUV<sub>max</sub> and SUV<sub>mean</sub>. HER2 immunohistochemistry was related to the quantitative <sup>89</sup>Zr-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. <b>Results:</b> In 200 patients, <sup>89</sup>Zr-trastuzumab uptake was quantified in 5,163 metastases, including 186 biopsied metastases. With increasing HER2 immunohistochemistry status, uptake was higher (geometric mean SUV<sub>max</sub> of 7.0, 7.6, 7.3, and 17.4 for a HER2 immunohistochemistry score of 0, 1, 2, or 3+, respectively; <i>P</i> < 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). <b>Conclusion:</b> 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.