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-operating-characteristic analysis. Results: In the 13 evaluable patients, correlation (R² ) between semiquantitative AR expression and ¹⁸F-FDHT uptake was 0.47 (P = 0.01) and between semiquantitative ER expression and ¹⁸F-FES uptake 0.78 (P = 0.01). The optimal cutoff for AR-positive lesions was an SUV_max of 1.94 for ¹⁸F-FDHT PET, yielding a sensitivity of 91% and a specificity of 100%; the optimal cutoff was an SUV_max 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 biopsy-associated sampling errors and heterogeneous receptor expression in breast cancer metastases.

Keywords: FDHT PET; FES PET; androgen receptor; breast cancer; estrogen receptor.