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.
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