EFFECT OF LETROZOLE ON BONE MARKERS AND BLOOD PRESSURE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 最近使用芳香酶抑制剂(AI)的研究表明，在绝经后妇女早期乳腺癌的他莫昔芬治疗5年后，无病生存率提高。AI是一类化合物，通过阻断芳香酶(一种细胞色素P450酶)来抑制雄激素合成雌激素，芳香酶催化雄激素外周转化为雌激素，从而将组织和血浆中雌二醇的浓度降低到去势以下的水平。 我们推测，随着雌二醇的抑制，最有效的芳香酶抑制剂来曲唑将导致骨吸收和骨形成标志物的显著增加，同时基线血压升高和夜间血压下降消失。将研究以下具体目标： 目的：探讨来曲唑对性激素水平的影响，以及性激素水平变化与骨标志物变化的关系。 测定骨吸收和骨形成标志物的变化。 观察来曲唑对24小时动态血压监测和办公室血压的影响。 测定来曲唑治疗前后神经认知功能参数的变化。 这将是一项为期12周的开放式标签试点研究，评估患有原发性乳腺癌的妇女，她们已经完成了5年的他莫昔芬治疗，并在咨询肿瘤医生后选择来曲唑作为治疗方法。这些患者将作为他们自己的对照。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Studies using aromatase inhibitors (AI) have recently demonstrated improved disease free survival after five years of tamoxifen therapy for early stage breast cancer in postmenopausal women. AI are a class of compounds that inhibit the synthesis of estrogens from androgens by blocking aromatase, a cytochrome P450 enzyme, which catalyzes the peripheral conversion of androgens to estrogens, thereby reducing the tissue and plasma concentration of estradiol to below castrate levels. We hypothesize that with suppression of estradiol, letrozole, the most potent aromatase inhibitor, will cause a significant increase in markers of bone resorption and bone formation, along with an increase in baseline blood pressure and loss of nocturnal dipping of blood pressure. The following specific aims will be studied: To determine the effects of letrozole on sex hormone levels and the relationship of change in sex hormone levels to the change in bone markers. To determine the change in markers of bone resorption and formation. To examine the effects of letrozole on 24 hr ambulatory blood pressure monitoring and office blood pressure. To determine change in parameters of neurocognitive function with letrozole therapy. This will be a 12 week, open label pilot study evaluating women with primary breast cancer, who have completed five years of tamoxifen treatment and are opting to choose letrozole as treatment in consultation with their oncologist. The patients will serve as their own controls.