Imaging of ER Density to Guide and Improve Tailored Therapy for Acquired Anti-hormonal Resistant Breast Cancer
|ClinicalTrials.gov Identifier: NCT01088477|
Recruitment Status : Completed
First Posted : March 17, 2010
Last Update Posted : May 21, 2014
|Condition or disease||Intervention/treatment|
|Breast Cancer||Other: Diagnostic intervention: Positron Emission Tomography with 16-alpha-[18-fluoro]-17betaestradiol|
The estrogen receptor (ER) is expressed in approximately 70% of the breast carcinomas. In general, for these patients anti-hormonal therapy is the therapy of first choice. Despite good responses in 50-60% of the patients, unfortunately all patients develop (acquired) resistance. Patients with acquired anti-hormonal resistance can be subdivided into three different groups: (1) patients that have lost ER-expression (~25%), (2) patients with preserved ER-expression (~55%) and (3) patients with enhanced ER-expression (~30%). Several studies suggest different treatment strategies for these three different ER-phenotypes in antihormonal resistant breast cancer. In patients with acquired anti-hormonal resistance, ~30% of the patients still respond to hormone-additive therapy with estrogens. In vitro studies have shown estrogen-induced apoptosis in long-treated estrogen deprived cells (simulating aromatase inhibitor resistance). It is suggested that this estrogen-hypersensitivity is accompanied by increased ER-expression.
Whole-body imaging of ER-density is now possible with positron emission tomography with the 16-alpha[18-fluoro]-17beta-estradiol tracer (FES-PET). FES-PET has shown to be a predictive biomarker for response to first line anti-hormonal therapy.
In this study we will include 50 patients, heavily pretreated with anti-hormonal therapy. All patients will undergo FES-PET at baseline and start estrogen therapy. Investigators and patients will be blinded for FES-PET results. Responders and non-responders will be defined using RECIST criteria and clinical follow-up. After response has been determined, FES-PET results will be analyzed. We hypothesize that patients responding to estrogen therapy can be identified on basis of high ER-expression determined by FES-PET.
|Study Type :||Observational|
|Actual Enrollment :||21 participants|
|Official Title:||Imaging of ER Density to Guide and Improve Tailored Therapy for Acquired Anti-hormonal Resistant Breast Cancer|
|Study Start Date :||February 2010|
|Primary Completion Date :||February 2014|
|Study Completion Date :||February 2014|
|Breast cancer patients with acquired anti-hormonal resistance||
Other: Diagnostic intervention: Positron Emission Tomography with 16-alpha-[18-fluoro]-17betaestradiol
In patients with acquired antihormonal resistance, eligible for estrogen therapy, a FES-PET scan will be made to determine FES-PET tumor uptake (which corresponds to estrogen receptor expression levels). Immediately after the FES-PET scan, all patients will start with a standard accepted dose of 2mg estradiol TID. Therapy response will be monitored by regular follow-up. RECIST criteria and clinical benefit will be used as criteria. In case of disease progression before end of the study period, estradiol treatment will be stopped.
- Quantifying FES-uptake to predict response to estrogen therapy [ Time Frame: 2 years ]
FES-uptake (prior to estrogen therapy) of tumour lesions will be recorded for all patients.
Patients will be prospectively categorized into responders and non-responders during standard follow-up (consisting of monthly visits, 3-monthly CT, and other techniques when indicated). Patients with complete response, partial response or stable disease for >6 months are defined as 'responders'.
With ROC analysis we will determine the optimal cut-off value for FES-uptake to predict response to estrogen therapy.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01088477
|University Medical Center Groningen|
|Groningen, Netherlands, 9700 RB|