PT  - JOURNAL ARTICLE
AU  - Eisses, Bertha
AU  - van Geel, Jasper J.L.
AU  - Brouwers, Adrienne H.
AU  - Bensch, Frederike
AU  - Elias, Sjoerd G.
AU  - Kuip, Evelien J.M.
AU  - Jager, Agnes
AU  - van der Vegt, Bert
AU  - Lub-de Hooge, Marjolijn N.
AU  - Emmering, Jasper
AU  - Arens, Anne I.J.
AU  - Zwezerijnen, Gerben J.C.
AU  - Vugts, Daniëlle J.
AU  - Menke-van der Houven van Oordt, C. Willemien
AU  - de Vries, Elisabeth G.E.
AU  - Schröder, Carolina P.
TI  - Whole-Body HER2 Heterogeneity Identified on HER2 PET in HER2-Negative, -Low, and -Positive Metastatic Breast Cancer
AID  - 10.2967/jnumed.124.267636
DP  - 2024 Oct 01
TA  - Journal of Nuclear Medicine
PG  - 1540--1547
VI  - 65
IP  - 10
4099  - http://jnm.snmjournals.org/content/65/10/1540.short
4100  - http://jnm.snmjournals.org/content/65/10/1540.full
SO  - J Nucl Med2024 Oct 01; 65
AB  - 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.