imaging of er density to guide and improve tailored therapy for acquired anti-hormonal resistant breast cancer

Conditions: Breast Cancer

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.

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.

Eligibility criteria:
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

Keywords: acquired anti-hormonal resistant breast cancer