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

Completed

• Conditions: Breast Cancer

• Registration Number: NCT01088477
• Lead Sponsor: University Medical Center Groningen

Brief Summary

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

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 Timeline

• Study Start: 2010-02
• Study First Submitted: 2010-03-16
• Study First Submitted QC: 2010-03-16
• Study First Posted: 2010-03-17
• Primary Completion: 2014-02
• Study Completion: 2014-02
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-03
• Last Update Posted: 2024-05-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 21

Inclusion Criteria

1. Patients with the diagnosis of acquired anti-hormonal resistant advanced breast cancer showing progression after two or more lines of antihormonal treatment;
2. Treatment with estradiol will be started;
3. Age> 18 years;
4. ECOG performance status 0-2.

Exclusion Criteria

1. Life Expectancy <3 months;
2. Uncontrolled CNS metastases;
3. History of thrombosis;
4. Uncontrolled hypercalcemia;
5. Treatment with any investigational drug within 30 days before start of study;
6. Serious uncontrolled concurrent illness, e.g. autoimmune disorders;
7. New York Hearth Association (NYHA) class III/IV congestive heart failure;
8. Dyspnea at rest due to any cause;
9. 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;
10. Women of childbearing potential unless a) surgically sterile or b) using adequate measures of contraception.
11. Diabetes Mellitus

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Quantifying FES-uptake to predict response to estrogen therapy	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.

Trial Locations

Locations (1)

University Medical Center Groningen; 🇳🇱 Groningen, Netherlands