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

18 Years
Open (Enrolling)
Breast Cancer

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Trial Information

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

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.

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

Type of Study:


Study Design:

Observational Model: Case-Only, Time Perspective: Prospective

Outcome Measure:

Quantifying FES-uptake to predict response to estrogen therapy

Outcome Description:

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.

Outcome Time Frame:

2 years

Safety Issue:



Netherlands: Medical Ethics Review Committee (METC)

Study ID:

RUG 2009-4529



Start Date:

February 2010

Completion Date:

September 2013

Related Keywords:

  • Breast Cancer
  • Acquired anti-hormonal resistant breast cancer
  • Breast Neoplasms