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 F-fluoroestradiol (F-FES) PET, and AR expression has been visualized in prostate cancer patients with F-fluorodihydrotestosterone (F-FDHT) PET. Our aim was to assess the concordance between F-FDHT andF-FES PET and tumor AR and ER expression measured immunohistochemically in patients with metastatic breast cancer. Patients with ER-positive metastatic breast cancer were eligible for the study, irrespective of tumor AR status. The concordance ofF-FDHT and F-FES uptake on PET with immunohistochemical expression of AR and ER in biopsies of corresponding metastases was analyzed. Patients underwentF-FDHT PET and F-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. In the 13 evaluable patients, correlation ( ) between semiquantitative AR expression and F-FDHT uptake was 0.47 ( = 0.01) and between semiquantitative ER expression and F-FES uptake 0.78 ( = 0.01). The optimal cutoff for AR-positive lesions was an SUV of 1.94 for F-FDHT PET, yielding a sensitivity of 91% and a specificity of 100%; the optimal cutoff was an SUV of 1.54 for F-FES PET, resulting in a sensitivity and specificity of 100% for ER.F-FDHT and F-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.

Breast Cancer: Evaluating Tumor Estrogen Receptor Status with Molecular Imaging to Increase Response to Therapy and Improve Patient Outcomes

“…While 18 F-FES imaging has many benefits, it does have some limitations related to its ability to detect liver metastases because of the increased uptake of 18 From a sensitivity and specificity perspective, 18 F-FES has a high accuracy for the detection of ER+ lesions; which was illustrated in a meta-analysis conducted on 12 different studies that evaluated patients who had 18 F-FES imaging and compared FES results to biopsy/histopathology staining (Allred) results in patients with breast cancer (30-32, [37][38][39][40][41][42][43][44][45]. The meta-analysis demonstrated that for metastatic lesions, a test sensitivity of 100% and a specificity of 99% (30-32, [37][38][39][40][41][42][43][44][45]. When combined (primary lesion + metastatic lesions), FES imaging resulted in a sensitivity of 81% and a specificity of 80% when compared to biopsy/histopathology results (30-32, 37-45).…”

Recent Advances in Imaging Steroid Hormone Receptors in Breast Cancer

“…In a metaanalysis of 5 18 F-fluoroestradiol imaging studies with ER immunohistochemistry results (143 patients), pooled sensitivity and specificity were 82% and 95%, respectively (6). In another study of 13 heavily pretreated patients with metastatic ER-positive breast cancer, Venema et al identified 1.54 as the optimal 18 F-fluoroestradiol SUV max cutoff to discriminate ER-positive from ER-negative lesions (7). In a retrospective study of 46 patients with histologically confirmed invasive breast cancer reported by Yang et al, the optimal 18 F-fluoroestradiol threshold was 1.21 for SUV mean and 1.82 for SUV max (8).…”

A risk‐based approach to identifying oligometastatic disease on imaging

“…Imaging data for these newer agents has been validated and shown to reflect target expression: a small but intensive study of targeted agents such as 18 F‐DHT and 18 F‐ES (Estradiol) showed that semi‐quantitative androgen or oestrogen receptor expression on immunohistochemistry and 18 F‐DHT or 18 F‐ES uptake respectively on PET was correlated. Moreover, using optimal cut‐offs (SUV max of 1.94 for 18 FDHT‐PET and 1.54 for 18 FES‐PET) sensitivities of 91% and 100% and specificities of 100% and 100% respectively were achieved …”

“…Moreover, using optimal cut-offs (SUV max of 1.94 for 18 FDHT-PET and 1.54 for 18 FES-PET) sensitivities of 91% and 100% and specificities of 100% and 100% respectively were achieved. 59 Whole-body MRI has the advantage of combining morphological data (T1 and T2-W imaging) with functional information (diffusion-weighted and dynamic contrast-enhanced imaging) thus simultaneously exploiting multiple contrast mechanisms to image and detect the presence of disease. As diffusion-weighted and contrast-enhanced MRI data are fundamentally quantitative, thresholding can be set so that the images display the required sensitivity and specificity.…”