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

Clasina M Venema, Lemonitsa H Mammatas, Carolina P Schröder, Michel van Kruchten, Giulia Apollonio, Andor W J M Glaudemans, A H H Bongaerts, Otto S Hoekstra, Henk M W Verheul, Epie Boven, Bert van der Vegt, Erik F de Vries, Elisabeth G E de Vries, Ronald Boellaard, Catharina Willemien Menke-van der Houven van Oordt, Geke Ap Hospers

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1906-1912
Number of pages7
JournalJournal of Nuclear Medicine
Volume58
Issue number12
Early online date14 Sep 2017
DOIs
Publication statusPublished - 1 Dec 2017

Cite this

Venema, C. M., Mammatas, L. H., Schröder, C. P., van Kruchten, M., Apollonio, G., Glaudemans, A. W. J. M., ... Hospers, G. A. (2017). Androgen and estrogen receptor imaging in metastatic breast cancer patients as a surrogate for tissue biopsies. Journal of Nuclear Medicine, 58(12), 1906-1912. https://doi.org/10.2967/jnumed.117.193649
Venema, Clasina M ; Mammatas, Lemonitsa H ; Schröder, Carolina P ; van Kruchten, Michel ; Apollonio, Giulia ; Glaudemans, Andor W J M ; Bongaerts, A H H ; Hoekstra, Otto S ; Verheul, Henk M W ; Boven, Epie ; van der Vegt, Bert ; de Vries, Erik F ; de Vries, Elisabeth G E ; Boellaard, Ronald ; Menke-van der Houven van Oordt, Catharina Willemien ; Hospers, Geke Ap. / Androgen and estrogen receptor imaging in metastatic breast cancer patients as a surrogate for tissue biopsies. In: Journal of Nuclear Medicine. 2017 ; Vol. 58, No. 12. pp. 1906-1912.
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title = "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 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.",
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Venema, CM, Mammatas, LH, Schröder, CP, van Kruchten, M, Apollonio, G, Glaudemans, AWJM, Bongaerts, AHH, Hoekstra, OS, Verheul, HMW, Boven, E, van der Vegt, B, de Vries, EF, de Vries, EGE, Boellaard, R, Menke-van der Houven van Oordt, CW & Hospers, GA 2017, 'Androgen and estrogen receptor imaging in metastatic breast cancer patients as a surrogate for tissue biopsies' Journal of Nuclear Medicine, vol. 58, no. 12, pp. 1906-1912. https://doi.org/10.2967/jnumed.117.193649

Androgen and estrogen receptor imaging in metastatic breast cancer patients as a surrogate for tissue biopsies. / Venema, Clasina M; Mammatas, Lemonitsa H; Schröder, Carolina P; van Kruchten, Michel; Apollonio, Giulia; Glaudemans, Andor W J M; Bongaerts, A H H; Hoekstra, Otto S; Verheul, Henk M W; Boven, Epie; van der Vegt, Bert; de Vries, Erik F; de Vries, Elisabeth G E; Boellaard, Ronald; Menke-van der Houven van Oordt, Catharina Willemien; Hospers, Geke Ap.

In: Journal of Nuclear Medicine, Vol. 58, No. 12, 01.12.2017, p. 1906-1912.

Research output: Contribution to journalArticleAcademicpeer-review

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

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 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 - 10.2967/jnumed.117.193649

DO - 10.2967/jnumed.117.193649

M3 - Article

VL - 58

SP - 1906

EP - 1912

JO - Journal of Nuclear Medicine

JF - Journal of Nuclear Medicine

SN - 0161-5505

IS - 12

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