Evaluation of [ 89 Zr]trastuzumab-PET/CT in differentiating HER2-positive from HER2-negative breast cancer

Abstract

Purpose

To evaluate whether tumor uptake of [⁸⁹Zr]trastuzumab can distinguish HER2-positive from HER2-negative breast cancer.

Methods

Women with HER2-positive (n = 34) and HER2-negative (n = 16) breast cancer underwent PET/CT 5 ± 2 days following [⁸⁹Zr]trastuzumab administration. HER2 status was determined based on immunohistochemistry and/or fluorescence in situ hybridization of primary or metastatic/recurrent tumor. Tumor [⁸⁹Zr]trastuzumab uptake was assessed qualitatively and semiquantitatively as maximum standardized uptake value (SUV_max), and correlated with HER2 status. Additionally, intrapatient heterogeneity of [⁸⁹Zr]trastuzumab uptake was evaluated.

Results

On a per-patient basis, [⁸⁹Zr]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_max 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_max was significantly higher in HER2-positive compared to HER2-negative patients (p = 0.003). A cutoff SUV_max 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 [⁸⁹Zr]trastuzumab uptake in 20% of patients with multiple lesions.

Conclusions

[⁸⁹Zr]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.

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