An Exploratory Study to Identify Potential Surrogate Endpoint Biomarkers That Are Modulated by Tamoxifen vs. Placebo in Women With an Increased Risk for Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 130
- 试验地点
- 8
- 主要终点
- Plasma levels of hormones and binding proteins as measured by ELISA, IHC, and TUNEL at baseline and 3 months
研究概览
简要总结
RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. The use of tamoxifen may be effective in preventing breast cancer.
PURPOSE: This randomized phase II trial is studying tamoxifen to see how well it works compared to placebo in preventing breast cancer in women who are at increased risk for the disease.
详细描述
OBJECTIVES:
- Compare molecular markers of proliferation and apoptosis in breast epithelial tissue of women at increased risk for breast cancer treated with tamoxifen vs placebo.
- Compare the modulation of markers of genomic instability in breast epithelial tissue of patients treated with these drugs.
- Compare serum levels of IGF-1, IGF-2, and IGFBP-3 of these patients at baseline and after treatment with these drugs.
OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to estimated 5-year breast cancer risk (1.67-5% vs ≥ 5%), presence of atypical ductal hyperplasia (yes vs no), and menopausal status (premenopausal vs postmenopausal). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive oral tamoxifen once daily.
- Arm I: Patients receive oral placebo once daily. Treatment in both arms continues for 3 months in the absence of invasive breast cancer or unacceptable toxicity.
Patients undergo core needle biopsy and fine needle aspiration biopsy at baseline and then at the completion of study treatment (for premenopausal patients); exactly 84 days after the first biopsy (for postmenopausal patients); or on the first or second day of the menstrual cycle on or after 84 days (during the third menstrual cycle) after the first dose of study medication (for patients with irregular menses).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 主要目的
- Prevention
- 盲法
- Double
入排标准
- 年龄范围
- 35 Years 至 120 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •At increased risk for breast cancer, as defined by 1 of the following criteria:
- •Histologically confirmed lobular carcinoma in situ (LCIS) treated by local excision only
- •Composite increased breast cancer risk of ≥ 1.67% over 5 years, based on the following criteria:
- •Number of first-degree female relatives with breast cancer
- •One or more prior breast biopsies
- •Fine-needle aspiration cytology of a non-cystic lesion in lieu of an open biopsy is considered a biopsy
- •Prior diagnosis of atypical hyperplasia of the breast
- •Age at first live birth
- •Nulliparity
- •Age at onset of menarche
- •No prior or suspected invasive breast cancer or ductal carcinoma in situ
- •No clinical evidence of malignancy by physical examination, including a breast examination within the past 3 months
- •No evidence of suspicious or malignant disease or uncharacterized lesions on bilateral mammogram within the past 6 months
- •Normal gynecologic examination, including a bimanual pelvic examination and, if indicated, pap smear within the past 12 months
- •Hormone receptor status:
- •Not specified
- •PATIENT CHARACTERISTICS:
- •35 and over
- •Menopausal status
- •Premenopausal and ovulating*, defined as having regular menses for the past 6 months OR irregular menses with follicular phase (i.e., day 3) follicle-stimulating hormone level < 20 mIU/mL OR
- •Postmenopausal NOTE: * Ovulation is determined by day 21 progesterone level > 3 ng/mL
- •Performance status
- •Life expectancy
- •Not specified
- •Hematopoietic
- •Complete blood count normal
- •No active bleeding disorder (e.g., qualitative or quantitative platelet abnormality, hemophilia, or von Willebrand's disease)
- •Liver function tests normal
- •Not specified
- •Cardiovascular
- •No prior deep-vein thrombosis except a single occurrence related to lower extremity trauma
- •No prior cerebral vascular accident
- •No prior transient ischemic attack
- •No prior pulmonary embolus except a single occurrence related to lower extremity trauma
- •No saline or silicone breast implants
- •No known allergy to tamoxifen
- •No macular degeneration
- •No malignancy within the past 5 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
- •No nonmalignant disease that would preclude administration of tamoxifen
- •No psychiatric condition, including a history of clinical depression or addictive disorder, that would preclude giving informed consent or study compliance
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective nonhormonal contraception during and for 3 months after study participation
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy
- •Not specified
- •Chemotherapy
- •No prior systemic adjuvant chemotherapy for LCIS
- •Endocrine therapy
- 另有 17 项未显示
排除标准
- 未提供
结局指标
主要结局
Plasma levels of hormones and binding proteins as measured by ELISA, IHC, and TUNEL at baseline and 3 months
Markers of proliferation and apoptosis in breast cells as measured by quantitative MSP at baseline and 3 months
Promoter-region methylation as assessed by microarrays at baseline and 3 months
Gene expression
次要结局
未报告次要终点