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, A H H
AU - Hoekstra, Otto S
AU - Verheul, Henk M W
AU - Boven, Epie
AU - van der Vegt, Bert
AU - de Vries, Erik F
AU - de Vries, Elisabeth G E
AU - Boellaard, Ronald
AU - Menke-van der Houven van Oordt, Catharina Willemien
AU - Hospers, Geke Ap
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
KW - Journal Article
U2 - https://doi.org/10.2967/jnumed.117.193649
DO - https://doi.org/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 -