Androgen and Estrogen Receptor Imaging in Metastatic Breast Cancer Patients as a Surrogate for Tissue Biopsies

Clasina M. Venema, Lemonitsa H. Mammatas, Carolina P. Schröder, Michel van Kruchten, Giulia Apollonio, Andor W. J. M. Glaudemans, Alfons H. H. Bongaerts, Otto S. Hoekstra, Henk M. W. Verheul, Epi Boven, Bert van der Vegt, Erik F. J. de Vries, Elisabeth G. E. de Vries, Ronald Boellaard, Catharina W. Menke van der Houven van Oordt, Geke A. P. Hospers*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

In addition to the well-known estrogen receptor (ER) and human epidermal growth factor receptor 2, the androgen receptor (AR) is also a potential drug target in breast cancer treatment. Whole-body imaging can provide information across lesions within a patient. ER expression in tumor lesions can be visualized by F-18-fluoroestradiol (F-18-FES) PET, and AR expression has been visualized in prostate cancer patients with F-18-fluorodihydrotestosterone (F-18-FDHT) PET. Our aim was to assess the concordance between F-18-FDHT and F-18-FES PET and tumor AR and ER expression measured immunohistochemically in patients with metastatic breast cancer. 

Methods: Patients with ER-positive metastatic breast cancer were eligible for the study, irrespective of tumor AR status. The concordance of F-18-FDHT and F-18-FES uptake on PET with immunohistochemical expression of AR and ER in biopsies of corresponding metastases was analyzed. Patients underwent F-18-FDHT PET and F-18-FES PET. A metastasis was biopsied within 8 wk of the PET procedures. Tumor samples with more than 10% and 1% nuclear tumor cell staining were considered, respectively, AR-and ER-positive. Correlations between PET uptake and semiquantitative immunohistochemical scoring (percentage positive cells x intensity) were calculated. The optimum threshold of SUV to discriminate positive and negative lesions for both AR and ER was determined by receiver-operating-characteristic analysis. 

Results: In the 13 evaluable patients, correlation (R-2) between semiquantitative AR expression and F-18-FDHT uptake was 0.47 (P = 0.01) and between semiquantitative ER expression and F-18-FES uptake 0.78 (P = 0.01). The optimal cutoff for AR-positive lesions was an SUVmax of 1.94 for F-18-FDHT PET, yielding a sensitivity of 91% and a specificity of 100%; the optimal cutoff was an SUVmax of 1.54 for F-18-FES PET, resulting in a sensitivity and specificity of 100% for ER. 

Conclusion: F-18-FDHT and F-18-FES uptake correlate well with AR and ER expression levels in representative biopsies. These results show the potential use of whole-body imaging for receptor status assessment, particularly in view of biopsy-associated sampling errors and heterogeneous receptor expression in breast cancer metastases.

Original languageEnglish
Pages (from-to)1906-1912
Number of pages7
JournalJournal of Nuclear Medicine
Volume58
Issue number12
DOIs
Publication statusPublished - 1-Dec-2017

Keywords

  • breast cancer
  • androgen receptor
  • estrogen receptor
  • FDHT PET
  • FES PET
  • PROSTATE-CANCER
  • PET
  • F-18-FLUOROESTRADIOL
  • HETEROGENEITY
  • 16-BETA-F-18-FLUORO-5-ALPHA-DIHYDROTESTOSTERONE
  • F-18-FDG
  • THERAPY
  • TUMORS

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