Imaging of ER Density to Guide and Improve Tailored Therapy for Acquired Anti-hormonal Resistant Breast Cancer

Study Overview
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Brief Summary
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In 50 breast cancer patients, heavily pretreated with anti-hormonal therapy, the investigators will evaluate the use of 16-alpha[18-fluoro]-17beta-estradiol positron emission tomography (FES-PET)as predictive biomarker for response to estrogen therapy.

Detailed Description
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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.

Official Title
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Imaging of ER Density to Guide and Improve Tailored Therapy for Acquired Anti-hormonal Resistant Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Other: Diagnostic intervention: Positron Emission Tomography with 16-alpha-[18-fluoro]-17betaestradiol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with the diagnosis of acquired anti-hormonal resistant advanced breast cancer showing progression after two or more lines of antihormonal treatment; Treatment with estradiol will be started; Age> 18 years; ECOG performance status 0-2. Exclusion Criteria: Life Expectancy <3 months; Uncontrolled CNS metastases; History of thrombosis; Uncontrolled hypercalcemia; Treatment with any investigational drug within 30 days before start of study; Serious uncontrolled concurrent illness, e.g. autoimmune disorders; New York Hearth Association (NYHA) class III/IV congestive heart failure; Dyspnea at rest due to any cause; Pregnant or lactating women. Documentation of a negative pregnancy test must be available for pre-menopausal women with intact reproductive organs and for women less than two years after menopause; Women of childbearing potential unless a) surgically sterile or b) using adequate measures of contraception. Diabetes Mellitus

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Breast cancer patients with acquired anti-hormonal resistance<br> | Other: Diagnostic intervention: Positron Emission Tomography with 16-alpha-[18-fluoro]-17betaestradiol<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantifying FES-uptake to predict response to estrogen therapy | 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. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acquired anti-hormonal resistant breast cancer