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Breast Cancer Res Treat. 2018 Jun;169(3):523-530. doi: 10.1007/s10549-018-4696-z. Epub 2018 Feb 13.

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

Author information

1
Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA. dehdashtif@wustl.edu.
2
Edward Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, USA. dehdashtif@wustl.edu.
3
Mallinckrodt Institute of Radiology, Campus Box 8223, 510 South Kingshighway Blvd., St. Louis, MO, 63110, USA. dehdashtif@wustl.edu.
4
Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA.
5
Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA.
6
Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
7
Department of Radiology, Yale University School of Medicine, New Haven, CT, USA.
8
Department of Radiaton Oncology, Washington University School of Medicine, St. Louis, MO, USA.
9
Departments of Radiology and Chemistry, University of Alabama at Birmingham, Birmingham, AL, USA.
10
Edward Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, USA.

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 (SUVmax), 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 SUVmax 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 SUVmax was significantly higher in HER2-positive compared to HER2-negative patients (p = 0.003). A cutoff SUVmax 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.

KEYWORDS:

Breast cancer; HER2; Positron emission tomography; Trastuzumab; Zirconium-89

PMID:
29442264
PMCID:
PMC5955803
DOI:
10.1007/s10549-018-4696-z
[Indexed for MEDLINE]
Free PMC Article

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