Androgen and estrogen receptor imaging in metastatic breast cancer patients as a surrogate for tissue biopsies

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 18F-fluoroestradiol (18F-FES) PET, and AR expression has been visualized in prostate cancer patients with 18F-fluorodihydrotestosterone (18F-FDHT) PET. Our aim was to assess the concordance between 18F-FDHT and 18F-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 18F-FDHT and 18F-FES uptake on PET with immunohistochemical expression of AR and ER in biopsies of corresponding metastases was analyzed. Patients underwent 18F-FDHT PET and 18F-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 · intensity) were calculated. The optimum threshold of SUV to discriminate positive and negative lesions for both AR and ER was determined by receiver-operatingcharacteristic analysis. Results: In the 13 evaluable patients, correlation (R2) between semiquantitative AR expression and 18F-FDHT uptake was 0.47 (P 5 0.01) and between semiquantitative ER expression and 18F-FES uptake 0.78 (P 5 0.01). The optimal cutoff for ARpositive lesions was an SUVmax of 1.94 for 18F-FDHT PET, yielding a sensitivity of 91% and a specificity of 100%; the optimal cutoff was an SUVmax of 1.54 for 18F-FES PET, resulting in a sensitivity and specificity of 100% for ER. Conclusion: 18F-FDHT and 18F-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 biopsyassociated sampling errors and heterogeneous receptor expression in breast cancer metastases.