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.
Observational Model: Case-Only, Time Perspective: Prospective
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.
Netherlands: Medical Ethics Review Committee (METC)