LOW DOSE TAMOXIFEN AND 4HPR IN EARLY BREAST CANCER

本项目的具体目标是寻求一种互动 小剂量他莫昔芬和合成维甲酸4-HPR之间的关系 绝经前原位妊娠妇女的替代终点生物标志物(SEB) 或微侵袭性乳腺癌。这将通过一个 采用2x2析因设计的双盲安慰剂对照试验， 女性将随机服用安慰剂或他莫昔芬，每天10毫克，或4- HPR，200毫克/天，或两种药物，为期两年。因为这两种药物都抑制了 第二原发癌发病率与循环胰岛素样生长因子-L水平的关系 在绝经前的妇女中，因为有大量证据表明 这种生长因子在糖尿病的病理生理机制中的重要作用 乳腺癌的主要预后指标是血浆胰岛素样生长因子-L的变化 经过两年的干预。另一个重要的终点是他的变化 在由定量评估的乳房X光密度百分比中 测量。次要终点是上皮异型增生的改变 经超声引导细针抽吸获得Ki67。 对侧乳房增加子宫内膜厚度的变化和 经阴道超声和输卵管引流术评价细胞增殖 吸引式刮宫。最后，对该组合的毒性进行了评价。 治疗方案是试验的一个重要目标。总共有300名女性 应在两年内累积，以检测到10 ng/ml的相互作用 两年后血浆胰岛素样生长因子-L和4%乳腺X线摄影密度 干预(力量=90%，双尾5%显著性)。这是合理的 假设血浆胰岛素样生长因子-L和胰岛素样生长因子的协同作用 乳房X光摄影密度可导致实质性的预防效果 乳腺癌的发生。SEBS的有效性将通过以下方式进一步评估 它们的基线相互关系以及 四个治疗组内这些SEB的变化。因此，该研究可能 提供有关联合治疗活动的基本信息 对乳腺癌的发生和子宫内膜的增殖可能导致 实施安全、成功的111期干预试验 旨在减少更广泛人群中的乳腺癌发病率-- 冒险的女人。

The specific aim of the present project is the search for an interaction between low-dose tamoxifen and the synthetic retinoid 4-HPR on a set of surrogate endpoint biomarkers (SEBs) in premenopausal women with in situ or minimally invasive breast cancer. This will be accomplished through a double-blind placebo controlled trial with a 2x2 factorial design, whereby women will be randomized to either placebo, or tamoxifen, 10 mg/day, or 4- HPR, 200 mg/day, or both agents for two years. Since both agents inhibit second primary breast cancer incidence as well as circulating IGF-l levels in premenopausal women and because there is substantial evidence for the critical role played by this growth factor in the pathophysiology of breast cancer, the main outcome measure is the change in plasma IGF-l after two years of intervention. Another important endpoint is he change in the percentage of mammographic density as assessed by quantitative measurement. Secondary endpoints are the change in epithelial dysplasia and Ki67 obtained by ultrasound-guided fine needle aspirate of the contralateral breast add the change in endometrial thickness and proliferation as valuated by transvaginal ultrasonography and pipelle aspiration curette. Finally, assessment of toxicity of the combination regimen is an important objective of the trial. A total of 300 women should be accrued in two years to detect an interaction of 10 ng/ml in plasma IGF-l and of 4% in mammographic density after two years of intervention (power = 90%, two-tailed 5% significance). It is reasonable to assume that a synergistic interaction upon plasma IGF-l and mammographic density could result in a substantial preventive effect on breast Carcinogenesis. The validity of SEBs will be further assessed by their baseline inter-relationships and also the correlations in the changes in these SEBs within the four treatment groups. The study may thus provide essential information on the activity of the combined treatment upon breast carcinogenesis and endometrial proliferation which may lead to the implementation of a safe and successful phase 111 intervention rial aimed at reducing breast cancer incidence in a broader population of at- risk women.