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Fluoroestradiol positron emission tomography reveals differences in pharmacodynamics of aromatase inhibitors, tamoxifen, and fulvestrant in patients with metastatic breast cancer.
- Source :
-
Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2011 Jul 15; Vol. 17 (14), pp. 4799-805. Date of Electronic Publication: 2011 Jul 12. - Publication Year :
- 2011
-
Abstract
- Purpose: To determine, by molecular imaging, how in vivo pharmacodynamics of estrogen-estrogen receptor (ER) binding differ between types of standard endocrine therapy.<br />Experimental Design: The ER has been a highly successful target for breast cancer treatment. ER-directed 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 (18)F-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.<br />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 (ρ = 0.63, P = 0.01).<br />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.
- Subjects :
- Adult
Aged
Breast Neoplasms diagnostic imaging
Breast Neoplasms pathology
Estradiol analysis
Estradiol metabolism
Estradiol therapeutic use
Female
Fulvestrant
Humans
Male
Middle Aged
Neoplasm Metastasis
Retrospective Studies
Uterus metabolism
Antineoplastic Agents, Hormonal therapeutic use
Aromatase Inhibitors therapeutic use
Breast Neoplasms drug therapy
Estradiol analogs & derivatives
Positron-Emission Tomography
Selective Estrogen Receptor Modulators therapeutic use
Tamoxifen therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1557-3265
- Volume :
- 17
- Issue :
- 14
- Database :
- MEDLINE
- Journal :
- Clinical cancer research : an official journal of the American Association for Cancer Research
- Publication Type :
- Academic Journal
- Accession number :
- 21750198
- Full Text :
- https://doi.org/10.1158/1078-0432.CCR-10-3321