TY - JOUR
T1 - Androgen and Estrogen Receptor Imaging in Metastatic Breast Cancer Patients as a Surrogate for Tissue Biopsies
AU - Venema, Clasina M.
AU - Mammatas, Lemonitsa H.
AU - Schröder, Carolina P.
AU - van Kruchten, Michel
AU - Apollonio, Giulia
AU - Glaudemans, Andor W. J. M.
AU - Bongaerts, Alfons H. H.
AU - Hoekstra, Otto S.
AU - Verheul, Henk M. W.
AU - Boven, Epi
AU - van der Vegt, Bert
AU - de Vries, Erik F. J.
AU - de Vries, Elisabeth G. E.
AU - Boellaard, Ronald
AU - van Oordt, Catharina W. Menke van der Houven
AU - Hospers, Geke A. P.
N1 - Copyright © 2017 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
KW - breast cancer
KW - androgen receptor
KW - estrogen receptor
KW - FDHT PET
KW - FES PET
KW - PROSTATE-CANCER
KW - PET
KW - F-18-FLUOROESTRADIOL
KW - HETEROGENEITY
KW - 16-BETA-F-18-FLUORO-5-ALPHA-DIHYDROTESTOSTERONE
KW - F-18-FDG
KW - THERAPY
KW - TUMORS
U2 - 10.2967/jnumed.117.193649
DO - 10.2967/jnumed.117.193649
M3 - Article
C2 - 28912144
SN - 0161-5505
VL - 58
SP - 1906
EP - 1912
JO - Journal of Nuclear Medicine
JF - Journal of Nuclear Medicine
IS - 12
ER -