Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Reproductive Control Agents

Fulvestrant

Estrogens

Estradiol 17 beta-cypionate

Estradiol 3-benzoate

Estradiol

Polyestradiol phosphate

Hormones

Hormone Antagonists

Contraceptive Agents

Contraceptive Agents, Hormonal

Contraceptive Agents, Female

Fluoroestradiol-PET is performed at baseline, after 1 month, and 3 months

A FES-PET/(CT) will be performed thrice during protocol execution. Patients will be injected with \~200MBq 18F-FES

Diagnostic intervention: Positron Emission Tomography with 16-alpha-[18-fluoro]-17betaestradiol

The dose of fulvestrant to optimally downregulate estrogen receptors (ER) is currently subject of debate. Effects of fulvestrant on the ERs may be evaluable by molecular imaging using positron emission tomography with the ER-specific FES tracer. In this pilot study we will evaluate the effects of the new dose of fulvestrant (500mg i.m.)on the availability of ER binding sites in 15 metastatic breast cancer patients.

The estrogen receptor (ER) is expressed in approximately 70% of the breast carcinomas. In these patients signaling via the ER induces proliferation and cell survival of malignant cells. Fulvestrant can inhibit this signaling route by blocking the receptor and decreasing ER-expression by increasing its turn-over rate.

The historical standard dose of fulvestrant was 250mg every 28 days i.m.; however studies performing serial biopsies showed that ER-downregulation was suboptimal. Recently the standard dose has been set to 500mg i.m. on day 1; 14; 28 and every 28 days thereafter. Although slightly more effective than the 250mg dose, still questions remain with respect to the required dose to establish maximal downregulation of ER-signaling.

Immunohistochemistry only provides static information, i.e. the level of ER-expression. However, dynamic information evaluating the effects of fulvestrant on occupancy of ERs, may also be valuable.

Whole-body imaging of the availability of ER binding sites using FES-PET may prove valuable to evaluate the effects of fulvestrant on the ER non-invasively in individual patients. This potentially allows adjustment of dosing in individual patients to aid therapy efficacy.

In this pilot-study we will evaluate 15 metastatic breast cancer patients. All patients will undergo FES-PET/CT at baseline, FES-PET after 1 month, and FES-PET/CT after three months. Hormone- and fulvestrant levels will be measured in all patients. Whenever possible, tumor biopsies will be performed to correlate to FES-PET results.

Molecular Imaging of Fulvestrant Effects on Availability of ER Binding Sites

In Vivo Imaging of the Effect of Fulvestrant on the Availability of Estrogen Receptor Binding Sites in Metastatic Breast Tumor Lesions Using FES-PET

FES-uptake will be calculated for all tumor lesions at baseline, 1 month and 3 months.

Changes between FES-uptake during fulvestrant therapy will be calculated for:

* 3 months minus baseline
* 3 months minus 1 month
* 1 month minus baseline

FES-uptake will be calculated for all tumor lesions at baseline, after 1 month and after 3 months.

Incomplete down-regulation/ occupancy of ERs is defined as 1) an absolute SUV\> 1.5, and 2) a relative decrease in SUV of \<75% during fulvestrant therapy.

The proportion of patients that match these criteria will be given for:

* 1 month minus baseline
* 3 months minus baseline

Liver metastases detected on PET/CT will be serially quantified at the 3 different time points to evaluate the feasibility to quantify liver lesions on FES-PET/CT

Patients will be categorized as responders and non-responders by standard follow-up (monthly visits, 3-monthly CT, other techniques when indicated).

The predictive value of FES-PET for response to fulvestrant will be calculated for:

* baseline FES-uptake
* changes in FES-uptake from baseline to 1 month
* changes in FES-uptake from baseline to 3 months

Lesion-based evaluation will be performed for measurable lesions as defined by RECIST criteria, and changes in diameter will be correlated to changes in FES-uptake at:

* 1 month minus baseline
* 3 months minus baseline

Explorative analysis to correlate several factors at different timepoints (baseline, 1 month, 3 months) to FES uptake.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Molecular Imaging of Fulvestrant Effects on Availability of ER Binding Sites	NCT01377324	Metastatic Brea...	Diagnostic inte...	18 Years -	University Medical Center Groningen
Molecular Imaging of Fulvestrant Effects on Availability of ER Binding Sites	NCT01377324	Metastatic Brea...	Diagnostic inte...	18 Years -	University Medical Center Groningen

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