Fluoroestradiol positron emission tomography reveals differences in pharmacodynamics of aromatase inhibitors, tamoxifen, and fulvestrant in patients with metastatic breast cancer

Hannah M. Linden, Brenda F. Kurland, Lanell M. Peterson, Erin K. Schubert, Julie R. Gralow, Jennifer M. Specht, Georgiana K. Ellis, Thomas J. Lawton, Robert B Livingston, Philip H. Petra, Jeanne M. Link, Kenneth A. Krohn, David A. Mankoff

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Abstract

Purpose: To determine, by molecular imaging, how in vivo pharmacodynamics of estrogen-estrogen receptor (ER) binding differ between types of standard endocrine therapy. Experimental Design: The ER has been a highly successful target for breast cancer treatment. ERdirected treatments include lowering ligand concentration by using aromatase inhibitors (AI) and blocking the receptor with agents like tamoxifen (TAM) or fulvestrant (FUL). We measured regional estrogen-ER binding by using positron emission tomography with 18F-fluoroestradiol (FES PET) prior to and during treatment with AI, TAM, or FUL in a series of 30 metastatic breast cancer patients. FES PET measured in vivo estrogen binding at all tumor sites in heavily pretreated women with metastatic bone soft tissue-dominant breast cancer. In patients with uterus (n = 16) changes in uterine FES uptake were also measured. Results: As expected, tumor FES uptake declined more markedly on ER blockers (TAM and FUL, average 54% decline) compared with a less than 15% average decline on estrogen-depleting AIs (P < 0.001). The rate of complete tumor blockade [FES standardized uptake value (SUV) ≤1.5] following TAM (5/5 patients) was greater than the blockade rate following FUL (4/11; 2-sided mid P = 0.019). Percent FES SUV change in the uterus showed a strong association with tumoral change (r = 0.63, P = 0.01). Conclusions: FES PET can assess the in vivo pharmacodynamics of ER-targeted agents and may give insight into the activity of established therapeutic agents. Imaging revealed significant differences between agents, including differences in the efficacy of blockade by different ER antagonists in current clinical use.

Original languageEnglish (US)
Pages (from-to)4799-4805
Number of pages7
JournalClinical Cancer Research
Volume17
Issue number14
DOIs
StatePublished - Jul 15 2011

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Aromatase Inhibitors
Tamoxifen
Estrogen Receptors
Positron-Emission Tomography
Breast Neoplasms
Estrogens
Uterus
Therapeutics
Neoplasms
Molecular Imaging
Research Design
fulvestrant
Ligands
Bone and Bones

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Fluoroestradiol positron emission tomography reveals differences in pharmacodynamics of aromatase inhibitors, tamoxifen, and fulvestrant in patients with metastatic breast cancer. / Linden, Hannah M.; Kurland, Brenda F.; Peterson, Lanell M.; Schubert, Erin K.; Gralow, Julie R.; Specht, Jennifer M.; Ellis, Georgiana K.; Lawton, Thomas J.; Livingston, Robert B; Petra, Philip H.; Link, Jeanne M.; Krohn, Kenneth A.; Mankoff, David A.

In: Clinical Cancer Research, Vol. 17, No. 14, 15.07.2011, p. 4799-4805.

Research output: Contribution to journalArticle

Linden, HM, Kurland, BF, Peterson, LM, Schubert, EK, Gralow, JR, Specht, JM, Ellis, GK, Lawton, TJ, Livingston, RB, Petra, PH, Link, JM, Krohn, KA & Mankoff, DA 2011, 'Fluoroestradiol positron emission tomography reveals differences in pharmacodynamics of aromatase inhibitors, tamoxifen, and fulvestrant in patients with metastatic breast cancer', Clinical Cancer Research, vol. 17, no. 14, pp. 4799-4805. https://doi.org/10.1158/1078-0432.CCR-10-3321
Linden, Hannah M. ; Kurland, Brenda F. ; Peterson, Lanell M. ; Schubert, Erin K. ; Gralow, Julie R. ; Specht, Jennifer M. ; Ellis, Georgiana K. ; Lawton, Thomas J. ; Livingston, Robert B ; Petra, Philip H. ; Link, Jeanne M. ; Krohn, Kenneth A. ; Mankoff, David A. / Fluoroestradiol positron emission tomography reveals differences in pharmacodynamics of aromatase inhibitors, tamoxifen, and fulvestrant in patients with metastatic breast cancer. In: Clinical Cancer Research. 2011 ; Vol. 17, No. 14. pp. 4799-4805.
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abstract = "Purpose: To determine, by molecular imaging, how in vivo pharmacodynamics of estrogen-estrogen receptor (ER) binding differ between types of standard endocrine therapy. Experimental Design: The ER has been a highly successful target for breast cancer treatment. ERdirected treatments include lowering ligand concentration by using aromatase inhibitors (AI) and blocking the receptor with agents like tamoxifen (TAM) or fulvestrant (FUL). We measured regional estrogen-ER binding by using positron emission tomography with 18F-fluoroestradiol (FES PET) prior to and during treatment with AI, TAM, or FUL in a series of 30 metastatic breast cancer patients. FES PET measured in vivo estrogen binding at all tumor sites in heavily pretreated women with metastatic bone soft tissue-dominant breast cancer. In patients with uterus (n = 16) changes in uterine FES uptake were also measured. Results: As expected, tumor FES uptake declined more markedly on ER blockers (TAM and FUL, average 54{\%} decline) compared with a less than 15{\%} average decline on estrogen-depleting AIs (P < 0.001). The rate of complete tumor blockade [FES standardized uptake value (SUV) ≤1.5] following TAM (5/5 patients) was greater than the blockade rate following FUL (4/11; 2-sided mid P = 0.019). Percent FES SUV change in the uterus showed a strong association with tumoral change (r = 0.63, P = 0.01). Conclusions: FES PET can assess the in vivo pharmacodynamics of ER-targeted agents and may give insight into the activity of established therapeutic agents. Imaging revealed significant differences between agents, including differences in the efficacy of blockade by different ER antagonists in current clinical use.",
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T1 - Fluoroestradiol positron emission tomography reveals differences in pharmacodynamics of aromatase inhibitors, tamoxifen, and fulvestrant in patients with metastatic breast cancer

AU - Linden, Hannah M.

AU - Kurland, Brenda F.

AU - Peterson, Lanell M.

AU - Schubert, Erin K.

AU - Gralow, Julie R.

AU - Specht, Jennifer M.

AU - Ellis, Georgiana K.

AU - Lawton, Thomas J.

AU - Livingston, Robert B

AU - Petra, Philip H.

AU - Link, Jeanne M.

AU - Krohn, Kenneth A.

AU - Mankoff, David A.

PY - 2011/7/15

Y1 - 2011/7/15

N2 - Purpose: To determine, by molecular imaging, how in vivo pharmacodynamics of estrogen-estrogen receptor (ER) binding differ between types of standard endocrine therapy. Experimental Design: The ER has been a highly successful target for breast cancer treatment. ERdirected treatments include lowering ligand concentration by using aromatase inhibitors (AI) and blocking the receptor with agents like tamoxifen (TAM) or fulvestrant (FUL). We measured regional estrogen-ER binding by using positron emission tomography with 18F-fluoroestradiol (FES PET) prior to and during treatment with AI, TAM, or FUL in a series of 30 metastatic breast cancer patients. FES PET measured in vivo estrogen binding at all tumor sites in heavily pretreated women with metastatic bone soft tissue-dominant breast cancer. In patients with uterus (n = 16) changes in uterine FES uptake were also measured. Results: As expected, tumor FES uptake declined more markedly on ER blockers (TAM and FUL, average 54% decline) compared with a less than 15% average decline on estrogen-depleting AIs (P < 0.001). The rate of complete tumor blockade [FES standardized uptake value (SUV) ≤1.5] following TAM (5/5 patients) was greater than the blockade rate following FUL (4/11; 2-sided mid P = 0.019). Percent FES SUV change in the uterus showed a strong association with tumoral change (r = 0.63, P = 0.01). Conclusions: FES PET can assess the in vivo pharmacodynamics of ER-targeted agents and may give insight into the activity of established therapeutic agents. Imaging revealed significant differences between agents, including differences in the efficacy of blockade by different ER antagonists in current clinical use.

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