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, A H H Bongaerts, Otto S Hoekstra, Henk M W Verheul, Epie Boven, Bert van der Vegt, Erik F de Vries, Elisabeth G E de Vries, Ronald Boellaard, Catharina Willemien Menke-van der Houven van Oordt, Geke Ap Hospers

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Abstract

In addition to the well-known estrogen receptor (ER) and the human epidermal growth factor receptor 2 (HER2), 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 18F-fluoroestradiol (FES) PET, and AR expression has been visualized in prostate cancer patients with 18F-fluorodihydrotestosterone (FDHT) PET. Our aim was to assess the concordance between FDHT- and FES-PET and tumor AR- and ER-expression measured immunohistochemically (IHC) in patients with metastatic breast cancer. Methods: Patients with ER-positive metastatic breast cancer were eligible for the study, irrespective of tumor AR-status. Concordance of FDHT and FES uptake on PET with IHC expression of AR and ER in biopsies of corresponding metastases was analyzed. Patients underwent FDHT-PET and FES-PET. A metastasis was biopsied within 8 weeks of the PET procedures. Tumor samples with >10% and >1% nuclear tumor cell staining were considered respectively AR- and ER-positive. Correlations between PET uptake and semi-quantitative IHC scoring (% 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 (ROC) analysis. Results: In the 13 evaluable patients correlation between semi-quantitative AR-expression and FDHT uptake was R²: 0.47 (P = 0.01) and between semi-quantitative ER-expression and FES uptake was R²: 0.78 (P = 0.01). The optimal cutoff for AR-positive lesions was a SUVmax of 1.94 for FDHT-PET, yielding a sensitivity of 91% and a specificity of 100% and for FES-PET a SUVmax of 1.54, resulted in a sensitivity and specificity of 100% for ER. Conclusion: FDHT and 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
Early online date14 Sep 2017
DOIs
Publication statusPublished - 1 Dec 2017

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