EFFECT OF LETROZOLE ON BONE MARKERS AND BLOOD PRESSURE

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。使用芳香化酶抑制剂（AI）的研究最近表明，绝经后早期乳腺癌妇女接受他莫昔芬治疗5年后，无病生存率得到改善。AI是一类通过阻断芳香化酶（一种细胞色素P450酶）抑制雄激素合成雌激素的化合物，芳香化酶催化外周雄激素向雌激素的转化，从而将组织和血浆雌二醇浓度降低到去势水平以下。我们假设，通过抑制雌二醇，来曲唑，最有效的芳香酶抑制剂，会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。研究的具体目的如下：确定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。目的探讨来曲唑对24小时动态血压监测和办公室血压的影响。目的探讨来曲唑治疗对神经认知功能参数的影响。这将是一项为期12周的开放标签试点研究，评估患有原发性乳腺癌的女性，她们已经完成了5年的他莫昔芬治疗，并在与肿瘤科医生协商后选择来曲唑作为治疗。这些病人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 catalyses 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.