Department of Breast Surgery And Department of Nuclear Medicine, Fudan University Shanghai Cancer Center,
试验速览
- 阶段
- 不适用
- 入组人数
- 130
- 试验地点
- 1
- 主要终点
- Clinical Objective Response
研究概览
简要总结
The aim of our current study was to analyze whether 18F-labeled Fluoromisonidazole (1-(2-nitro-1-imidazolyl)- 2-hydroxy-3-fluoropropane [18F-FMISO]) PET/CT and expression of HIF-1-alpha could predict response of primary endocrine therapy in ER-positive breast cancer
详细描述
Approximately 30% of ER-positive breast cancer will unfortunately display primary resistance to hormonal therapy, and some may develop acquired resistance to the therapy after initial treatment. Hypoxia is a normal phenomenon in solid tumors that arises, in part, from uncontrolled proliferation and immature blood vessels. Previous studies have demonstrated hypoxia significantly reduced both the growth-promoting effects of estradiol (E2) and the growth-inhibitory effects of an antiestrogen on ER-positive breast cancer cell lines. A recent study comparing neoadjuvant letrozole with letrozole plus metronomic cyclophosphamide found that increased levels of HIF-1a were significantly associated with resistance to treatment. Taken together, these data indicate that hypoxia might be associated with endocrine resistance in breast cancer.
With PET/CT, radiolabeled hypoxia-avid compounds can be applied to evaluate oxygenation status in experimental or human tumors. 18F-labeled fluoromisonidazole (1-[2-nitro- 1-imidazolyl]-2-hydroxy-3-fluoropropane [18F-FMISO]) PET/CT is the most widely used one in the clinic. Studies have demonstrated an excellent correlation between the 18F-FMISO uptake and oxygenation status of several cancers including breast cancer.
The major aim of our study was to analyze uptake of 18FFMISO as well as the IHC expression of HIF-1-alpha in ER-positive breast cancers, and to predict the clinical, pathological and biological response of primary endocrine therapy.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 60 Years 至 90 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Postmenopausal female
- •With primary invasive ER positive breast cancer pathologically approved by core needle biopsy
- •The target lesion must be measurable and maximum diameter should be over 2cm.
- •Require and accept Endocrine therapy
- •Never treated with endocrine therapy before
- •Patients must have an ECOG performance status of 0 to 2
- •Leucocyte count must be ≥ 3.0*10^9/L and platelet count must be ≥ 40*10^9/L; AST/SGOT or ALT/AGPT must be < 2 times the ULN; serum creatinine must be < 2 times the ULN
排除标准
- •Patients with brain and liver metastasis
- •Previous history of severe heart dysfunction (above Class III), infection, osteoporosis, bone related event or disease in endocrine system
- •Combination of other anticancer therapy, with the exception of biphosphonate
研究组 & 干预措施
Hypoxic Group
Higher 18FMISO uptake (Target to background Ratio, TBR>1.2) in Primary breast cancer by 18FMISO PET/CT scan.Primary endocrine therapy Letrozole was given to the patients.
干预措施: 18FMISO PET/CT scan (Other)
Hypoxic Group
Higher 18FMISO uptake (Target to background Ratio, TBR>1.2) in Primary breast cancer by 18FMISO PET/CT scan.Primary endocrine therapy Letrozole was given to the patients.
干预措施: Letrozole (Drug)
Non-Hypoxic Group
Lower 18FMISO uptake (TBR<1.2)in primary breast cancer by 18FMISO PET/CT scan.Primary endocrine therapy letrozole was given to the patients.
干预措施: 18FMISO PET/CT scan (Other)
Non-Hypoxic Group
Lower 18FMISO uptake (TBR<1.2)in primary breast cancer by 18FMISO PET/CT scan.Primary endocrine therapy letrozole was given to the patients.
干预措施: Letrozole (Drug)
结局指标
主要结局
Clinical Objective Response
时间窗: 4 months
Tumor response was evaluated according to the criteria of the World Health Organization. Clinical tumor progression (PD) was defined as an increase of at least 25% in tumor size; stable disease (SD) as an increase of less than 25% or a reduction of less than 50%; partial response (cPR) as a tumor shrinkage greater than 50%; and complete response (cCR) as the complete disappearance of all clinical signs of disease.
次要结局
- Pathological Response(4 months)
- Depression of Ki67 score(3 months)
研究者
Guangyu Liu
Deputy director of Department of Breast Surgery,Cancer Hopital & Institute
Fudan University