Imaging of ER Density to Guide and Improve Tailored Therapy for Acquired Anti-hormonal Resistant Breast Cancer
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|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|
|Actual Primary Completion Date :||February 2014|
|Actual 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01088477
|University Medical Center Groningen|
|Groningen, Netherlands, 9700 RB|