In Vivo Imaging of the Effect of Fulvestrant on the Availability of Estrogen Receptor Binding Sites in Metastatic Breast Tumor Lesions Using FES-PET
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.
Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic
Visualize and quantify changes in FES uptake in tumor lesions during fulvestrant 500mg therapy
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
baseline; 1 month; 3 months
Netherlands: Medical Ethics Review Committee (METC)