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. 2024 Oct 1;65(10):1540-1547.
doi: 10.2967/jnumed.124.267636.

Whole-Body HER2 Heterogeneity Identified on HER2 PET in HER2-Negative, -Low, and -Positive Metastatic Breast Cancer

Bertha Eisses  1 , Jasper J L van Geel  1 , Adrienne H Brouwers  2 , Frederike Bensch  1 , Sjoerd G Elias  3 , Evelien J M Kuip  4 , Agnes Jager  5 , Bert van der Vegt  6 , Marjolijn N Lub-de Hooge  2   7 , Jasper Emmering  8 , Anne I J Arens  9 , Gerben J C Zwezerijnen  10 , Daniëlle J Vugts  10 , C Willemien Menke-van der Houven van Oordt  11 , Elisabeth G E de Vries  1 , Carolina P Schröder  12   13
Affiliations

Whole-Body HER2 Heterogeneity Identified on HER2 PET in HER2-Negative, -Low, and -Positive Metastatic Breast Cancer

Bertha Eisses et al. J Nucl Med. .

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 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 SUVmax and SUVmean 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 SUVmax 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.

Keywords: 89Zr-trastuzumab PET; HER2; breast cancer; diagnostic performance; human epidermal receptor 2; metastases.

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