Combination of Low Dose Antiestrogens With Omega-3 Fatty Acids for Prevention of Hormone-independent Breast Cancer
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 266
- 试验地点
- 1
- 主要终点
- Change in Absolute Breast Density
研究概览
简要总结
The overall hypothesis is that the combination of a low dose of the antiestrogen Raloxifene with omega-3 fatty acids will exert a synergistic breast cancer chemopreventive effect due to the crosstalk of their downstream cellular effects leading to decreased proliferation and increased apoptosis of premalignant mammary cells. Based on the investigators hypothesis that upregulation of functional estrogen receptors in the premalignant lesions is also responsible for the development of hormone independent tumors, the investigators postulate that the combination of antiestrogens and omega-3 fatty acids will reduce the development of both hormone-dependent and -independent tumors. At present, there are no known interventions able to decrease the development of hormone-independent tumors, which are more prevalent, more aggressive, leading to the patient's demise. In addition, the investigators postulate that this approach will be safe since it will combine a lower and hence a less toxic dose of Raloxifene with the administration of omega-3 fatty acids which are known to have health benefits, i.e., reduction in cardiovascular risk, beyond their possible chemo preventive effect in breast cancer.
详细描述
The main objectives of this study are to determine the individual and combined effects of Raloxifene and omega-3 fatty acids on surrogate markers of breast cancer development in healthy, postmenopausal women. The primary endpoint will be mammographic density for which the study has been powered. Breast density is a major risk factor for breast cancer and hence it is chosen to evaluate the potential chemopreventive efficacy of our interventions. Secondary endpoints would include markers of oxidative stress, parameters of estrogen metabolism, markers of inflammation, and markers of IGF-I signaling, all of which have been shown in the literature to have an influence on mammary carcinogenesis.
Study Population: Healthy, postmenopausal women between the ages of 35-70 years, undergoing yearly mammograms as part of routine screening practice.
Method of Identification of Subjects/Samples/Medical Records: Women reporting for yearly mammograms will be considered for this protocol. They will be given first a screening questionnaire to rule out any co-existing medical condition that would predispose them to thromboembolic events.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 35 Years 至 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Postmenopausal status defined as history of at least 12 months without spontaneous menstrual bleeding or a documented hysterectomy and bilateral salpingo oophorectomy
- •Breast density greater than 25%
- •No hormone replacement therapy for at least six months prior to entry into this study
- •Non-smokers.
排除标准
- •History of stroke, pulmonary embolism or deep vein thrombosis
- •History of atherosclerotic heart disease
- •Presence of any known hypercoagulable state either congenital (e.g., protein S deficiency) or acquired (e.g., corticosteroid treatment)
- •Diabetes mellitus
- •Uncontrolled hypertension (BP ≥140/90)
- •Presence of a psychiatric condition that would interfere with adherence to the protocol.
研究组 & 干预措施
Group 2: Raloxifene 60 Mg Oral Tablet
Raloxifene 60 mg Orally Daily
干预措施: Raloxifene 60 Mg Oral Tablet (Drug)
Group 3: Raloxifene 30 Mg Oral Tablet
Raloxifene 30 mg Orally Daily
干预措施: Raloxifene 30 Mg Oral Tablet (Drug)
Group 4: Lovaza 4 gm oral
Lovaza 4 gm/day Orally with Meals
干预措施: Lovaza 4gm oral (Dietary Supplement)
Group 5: Lovaza 4gm & Raloxifene 30mg
Lovaza 4 gm/day oral capsule with meals plus Raloxifene 30 mg oral tablet daily
干预措施: Lovaza 4gm & Raloxifene 30mg (Drug)
结局指标
主要结局
Change in Absolute Breast Density
时间窗: 2 years
Change of absolute breast density as indicated by mammography from baseline to Year +1 and completion of study (Year +2). No other mammograms will be obtained or used for the purpose of this study. Absolute breast density volume is based on breast thickness and the x-ray attenuation at each pixel of the image.
次要结局
- Changes in Biomarkers for Oxidative Stress:Urinary 8-(Isoprostane) F-2α(1 year)
- Changes in Biomarkers for Oxidative Stress: Urinary 8-hydroxy-deoxyguansine(1 year)
- Changes in Complete Blood Count: Hemoglobin(2 years)
- Changes in Biomarkers for Estrogen Metabolism: 2-hydroxy Estrone (Urinary 2-OHE1) and 16-α-hydroxy Estrone (16α-OHE1)(1 year)
- Changes in Insulin-like Growth Factor-1 (IGF-1) and Insulin-like Growth Factor-1 Binding Protein-3 (IGFBP-3)(1 year)
- Changes in Serum Lipid Levels(2 years)
- Changes in Complete Blood Count: White Blood Cells and Platelets(2 years)
- Changes in Serum Biomarkers for Inflammation From Levels of High Sensitivity C-reactive Protein (hsCRP) and Interleukin 6 (IL-6)(1 Year)
- Changes in Complete Blood Count: Red Blood Cells(2 years)
- Changes in Complete Blood Count: Hematocrit(2 years)
研究者
Andrea Manni
Professor and Chief Division of Endocrinology, Diabetes, and Metabolism
Milton S. Hershey Medical Center