Imaging of ER Density to Guide and Improve Tailored Therapy for Acquired Anti-hormonal Resistant Breast Cancer
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- Quantifying FES-uptake to predict response to estrogen therapy
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
结局指标
主要结局
Quantifying FES-uptake to predict response to estrogen therapy
时间窗: 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.
次要结局
未报告次要终点